5. Biological
effects of ionizing radiation
Radiation protection
5.1. Effects of radiation on matter. Basic quantities of dosimetry
5.2. Biological effects of ionizing radiation
5.3. Objectives and methods of radiation
protection
5.4. Radiation monitoring and personal dosimetry
5.5. Open radionuclides. External and internal contamination
5.6. Radiation protection in workplaces with
ionizing radiation
5.7. Radiation exposure during radiation
diagnosis and therapy
5.8. Legislative provision of radiation
protection
5.1. Effects of radiation on matter. Basic quantities of dosimetry
Physico-chemical
effects of ionizing radiation
In §1.6 "Ionizing radiation" we dealt in detail with
the properties of different types of radiation and its
interactions with the substance environment; however, it was
mainly from the point of view of radiation physics
, ie the influence of the material environment on the propagation
of radiation, its absorption, scattering or conversion to other
types of radiation. Here we will deal with radiation interactions
from the point of view of the substance itself exposed to
radiation, ie the effects of radiation on the
physical and chemical properties of the substance. Special
attention will be paid to the effects of radiation on living
tissue .
The very name "ionizing
radiation" (see definition in §1.6) suggests that the basic
physical effect of this radiation on every substance is ionization
- Negative electrons are ejected from the originally electrically
neutral atoms, which turns these atoms into positively charged
ions. The effect of this ionization on the irradiated substance
decisively depends on its atomic composition :
Irradiation
of the element - no chemical change
If the irradiated substance is an element
composed of the same atoms, they recombine the
released electrons with positive ions to form again the
same atoms of the element as before irradiation. Chemical
and physical changes are either no or
insignificant *); examples are the formation of atomic
oxygen and ozone during the irradiation of oxygen gas O 2 , or changes
in the crystal structure of elements in the solid phase.
*) All this applies to
"ordinary" types of radiation a, b, g of usual
energies, where interactions occur at the level of the
atomic shell. Interaction of radiation whose quantum they
havevery high energy (higher than about
tens of MeV), or neutron radiation ,
causes changes in the nuclei of the atoms of the
irradiated material - there are physical (and induced
chemical) changes , including the activation
of originally non-radioactive substances.
We also do not consider the situation of extremely high
fluxes of radiation , where the absorbed energy
can lead to melting or evaporation
of the irradiated substance (this can happen,
for example, with targets irradiated in an accelerator).
Irradiation
of a compound ® chemical changes
However, if the irradiated substance is a compound
, a particularly complex organic substance, ionization of
atoms can lead to a number of chemical changes
and reactions :
1. Ionized atoms are released
from chemical bonds, molecules dissociate
. Decomposition of compounds by ionizing radiation is
called radiolysis .
2. Atoms and molecules released during
radiolysis are usually not neutral, but ionized and have
unpaired electrons - highly reactive radicals are
formed. They can further chemically react with
the molecules of the substance, their oxidizing and
reducing effects can break the internal molecular bonds
and change the chemical structure of the molecules - new
compounds are formed .
Thus, upon
irradiation of the compound, some of the original
molecules are decomposed, whereas new molecules appear
that were not previously available. The more complex the
irradiated substance, the more diverse the chemical
changes and reactions in it. The most complex chemicals
are contained in living organisms .
Thus, when irradiated living tissue, very diverse complex
(bio) chemical reactions occur, which can result in biological
changes at the level of cells and whole
organisms.
Basic
quantities of dosimetry
Dosimetry of ionizing radiation is a field of radiation
physics, which deals with the effects of radiation on substances
in relation to the types and properties of radiation interaction
with matter and the amount of radiation absorbed in matter
(absorbed energy - "dose"). The studied substance is
mainly living tissue , model measurements of
doses and dose rates are performed in water, air and special dosimetric
phantoms . It follows the physical mechanisms of interaction
of radiation with substances, discussed in detail in §1.6 "
Ionizing
radiation ".
Absorbed
radiation dose
The rate of physicochemical effects of radiation
on a substance - as well as the induced biological
effects, if the irradiated substance is living tissue -
it is proportional to the concentration of ions
formed in a given volume of the substance. And this concentration
of ions, in turn, is proportional to the energy
that has been transferred to the substance in
the given volume by radiation .
This initial
dosimetric quantity, called transmitted or communicated
energy E, represents the energy [J,
eV] which the ionizing radiation has transmitted to the
substance in a certain volume. It is generally given by
three components: E = S E in - S E out + S E nucl . S E in
is the sum of the energies of all
ionizing particles that have entered the given volume. S E out is the sum of the
energies of all particles that have left the given volume. S E nucl is the sum of all
possible changes in the rest energies of nuclei and particles
that occurred in the considered volume during the event. nuclear
transformations caused by the effects of radiation (in practice,
with the exception of high-energy radiation of about 10 MeV and
higher, this third component is zero). This quantity has only a
"school" meaning and is not used in dosimetric practice
...
The basic dosimetric
quantity, which characterizes the physico-chemical and later
biological effects of radiation on the substance, is the absorbed
radiation dose :
Absorbed
dose (abbreviated
as "dose") D
is the energy of ionizing radiation absorbed at a given
location of the irradiated substance per unit mass. It is
thus given by the ratio
D =
D E / D m,
where D E is the mean energy of the ionizing radiation
absorbed in the volume element of the substance and D m is the
mass of this volume element. Unit of absorbed dose is 1 J
/ 1 kg, which is called one Gray [Gy]
(sub-unit then 1mGy = 10 -3 Gy and 1 m Gy = 10 -6 Gy).
This basic
dosimetric unit was named in honor of the English
radiologist RHGray (1905-1965), who in the 30s-50s
intensively dealt with the interactions of radiation with
matter and the effects of radiation on living tissue (including tumor tissue - examined, among other
things, the so-called oxygen effect , mentioned
below in §5.2, the text under Fig.5.2.2) . The older unit of radiation dose (in the CGS
system) was 1 rad = 10 -2 Gy ( rad = r
adiation and bsorbed d
axis ) .
Since the majority of the absorbed
energy ultimately changes into heat , we
are characterized by the absorbed dose and the amount of
transferred thermal energy - heating of
the irradiated material. However, at doses used in
biological applications, this radiation heating is
negligible.
Dose
rate D´
is the dose received at a given site by the irradiated
substance per unit time, ie the ratio of the dose
increment D D for the time interval D t:
D´
= D D / D t.
The unit is Gray per second [Gy.s -1 ], in practice the units [Gy / min.] or [mGy /
hour] are used more often.
The size of the dose or dose rate
depends on the intensity of radiation at the irradiated
site (it is directly proportional to the fluctuation of
radiation), the type and energy of quantum ionizing
radiation, as well as the properties of interaction and absorption
of this radiation in the substance. Although the radiation
dose is a physical quantity that is basically applicable
to various substances and materials, in radiation
dosimetry it is used mainly in biological
applications - it is mainly determined for soft
tissues or water . And so it is for all the
dosimetric quantities listed below.
Note: The
amount of radiation doseis introduced to express the
degree of usual (obvious, macroscopic) effects of radiation on
matter - ie absorbed energy, which is manifested by
physico-chemical changes at the level of electron shells, or by
increasing the kinetic energy of the movements of atoms and
molecules in matter. In rare cases, however, the energy of the
radiation can be absorbed by the atomic nucleus in a way that is
not directly reflected at the atomic level. This is especially
the case with neutron radiation, where some neutrons can be
absorbed by the nuclei of the irradiated substance to form a
heavier isotope. This does not affect the normal physicochemical
properties of the substance, but only the increase in the mass of
some atoms. It is debatable whether this part of the absorbed
energy should be included in the radiation dose. The situation is
even more complicated here: nuclei that have absorbed neutrons
are often radioactive ( activation occurs)) and during
their transformations considerable energy is subsequently
released, causing a radiation load.
Exposure,
kerma, Terma
When evaluating the effect of indirectly ionizing radiation on
the substance we can still meet celebrity exposure and kerma
, especially in the older literature:
¨ Kerma
(Eng .: abbreviation of the
inetic e nergy r
eleased in ma rial
- kinetic energy released in material) is very similar to the
definition of K = D E / D m and the same unit [Gy] as the absorbed dose, while for
DE
takes the sum of initial kinetic energies of the charged
particles released as a result of interaction of the particles of
the primary radiation in the intended volume of the solid mass D m. Kerma is
introduced because the basic definition of dosages comprising
only released directly ionizing particles gave no information on
what occurs in the vicinity of the monitored volume of the
substance, especially in the case of secondary indirect ionizing
radiation. For charged primary particles, there is no difference
between the kerma and the dose (for radiation generated by
charged particles, the kerma is not even defined). Even for
indirectly ionizing radiation in the equilibrium state
*), when the secondary radiation is absorbed, K = D applies; only
in non-equilibrium processes, near the surface of the substance
or at high energies, when part of the radiation can escape, will
K ¹D,
while the differences are not large in practice. The relationship
D = K (1- g ) applies between the dose and the kerma , where g is the fraction of
the energy of the released charged particles that is lost during
the radiation processes in the material. For X-rays and gamma
rays with an energy less than 3MeV, the values ??of both
quantities (kerma and dose) practically coincide, the value of g is only fractions
of a percentage.
*) Electron equilibrium is
a state where the energy released by the primary radiation in a
given elementary volume of matter is as great as the energy
transmitted there by the secondary electrons. This balance is
disturbed at the surface of the substance and around the
interface of two different environments. Upon penetration of the
primary indirectly ionizing quantum (photon) into the
environment, the released energy is carried away by secondary
electrons and can be absorbed at a greater depth. At low energies
(X-rays), the decay of the secondary electrons is very small and
the energy is absorbed almost immediately at the point of release
from the interaction of the primary particle - the electron
equilibrium is met and the dose value is numerically the same as
kerma. In the high-energy g-radiation carries the secondary electrons to the
released energy to a greater depth - the dose shows an initial
rise and only at a greater depth does the electron equilibrium
occur and the dose follows the kerma with its value.
In the case of
indirectly ionizing radiation (photons g , neutrons), the kerma
characterizes the energy transferred to the charged particles in
matter (electrons and protons), especially during the first
collision. Kerma depends only on the interactions of the primary
radiation in the material of the mass element D m, while the
absorbed dose also depends on the secondary particles
that were formed around the analyzed volume element and entered
this mass element Dm (when they were partially or completely absorbed). For
kerma, it is necessary to specify to which substance it relates
(eg kerma in air or kerma in tissue).
Rather, Kerma expresses the
properties of the radiation beam through interactions with the
medium, while dose expresses the effect on the irradiated
environment. If kerma is introduced in the same given material
environment, mostly in air, it can be used to quantify the
"yield" of radiation sources, the kerma power
is proportional to the fluctuation of the radiation .
In recent literature occurs, although rarely variable Terma
:
¨ TERMA ( T
otal E nergy R
eleased per unit MAss
- total energy released per unit mass of material) has
practically the same definition of T = D E / D m and the same unit [Gy] as
the absorbed dose. It is a multiple of the mass attenuation
coefficient ( m / y ) and the primary fluctuation [MeV / cm 2 ] of the radiation
energy at a given location.
If the balance of charged particles is
reached during the interaction of the radiation beam, there is no
difference between the quantities of therma and dose
(or their relationship is linear). However, differences may occur
at the interface of different substances or at the edges of the
bundle.
¨ Exposure is
defined as the ratio of the absolute value D Q of the total electric
charge of single-sign ions which have been released by the
interaction of photons (X or gamma) in a mass element of air
of mass D m, with complete braking of all electrons and positrons
formed: D Q / D m, based on the unit mass of this air. The unit of
exposure in the SI system is the coulomb per kilogram [C.kg -1 ] *). Only the
charge of ions released by the interaction of primary photons and
the interaction of secondary electrons released from air atoms is
included in this total electric charge D Q, not including another
charge which may arise from the absorption of bremsstrahlung
emitted by electrons (or characteristic X-rays). For high energy
photons g(higher than 2-3MeV), where the additional ionization
caused by the bremsstrahlung cannot be neglected, the magnitude
of the exposure no longer objectively captures the effect of such
radiation.
*) Rentgen R
The former unit of exposure in the system of CGS
units ( C entimeter- G ram- S
ekunda) was rentgen R : It is
the amount of radiation at which 1 electrostatic unit is released
by ionization ( 1 esu » 3,3.10 -10 C) charge in 1cm 3 of dry air (under normal conditions of temperature and
pressure). The conversion relationship is 1R =
0.258 C.kg -1 .
The exact radiation dose absorbed by
a substance other than air cannot be determined completely
objectively from the exposure value, because the absorbed
radiation dose depends on the properties of the material and on
the type and energy of the radiation. For gamma and X rays with
normal energies of tens to hundreds of keV, a dose of
approximately 0.01 Gray (1 Rad) is absorbed upon
exposure to 1 X-ray in human tissue . In simple
terms, the conversion relationship applies: 1 rentgen » 10
mSv . In the various radiation tables, the conversion
factor between X-rays and Sieverts is given in the range 1 R =
(0.0087-0.0096) Sv.
As with the radiation dose and exposure kerma also defines kermový
power and exposure rate, as increment of kerma or
exposure per unit time (1 second); the word "speed" was
previously used instead of the word "power".
Both of these quantities,
exposure and kerma, are mostly abandoned in
dosimetric practice , they are still used marginally in the
primary standardization of radiation beams (eg in radiotherapy,
radiodiagnostics). However, in the literature in the field of
radiodiagnostics and radiotherapy, terminology often persists.
For monitoring X-rays in X-ray diagnostics, eg "input kerm
input in air" is used.
Terminological note:
We use the word " exposure
" in our materials from nuclear and radiation physics in its
general scientific meaning: lighting - the degree of irradiation
of an object or material, exposure (or
exposure time) during a photograph or other
radiation image. It has almost nothing to do with the
above-mentioned older abandoned dosimetric quantity!
Radiation dose from radioactivity
External
radionuclide source
Radionuclides are
common sources of ionizing radiation in practice (§1.2 " Radioactivity ") . Radionuclide sources
are most often made in the form of encapsulated (closed) external
radioactive emitters . The radioactive
emitter emits its radiation (given by the type of radioactive
transformations and activity) isotropically in all
directions, up to a full spatial angle of 4 p . With the distance r
from the source, the radiation "dilutes", it is
distributed on an imaginary sphere with an area S = 4p r 2 . Radiation
intensity I (fluence of quanta) emitted by a
radioactive source is therefore directly proportional to the
activity of preparation A and indirectly proportional to
the square of the distance r from the source (this is exactly true for a spot emitter, approximately
in situations where the distance is significantly greater than
the source) :
I
= G . A / 4p r 2 ,
where G is the number of quanta emitted by the radionuclide per
decay.
The same applies to the energy fluctuation determining
the radiation dose. The amount of energy W [J / s] emitted by a
radioactive emitter per unit time (1 s.) Is given by the product
of activity A[Bq] and mean energy <E> [eV] quantum
emitted per 1 decay: W = G.A <E> .1,6.10 -19 (coefficient 1,6.10 -19 is the conversion factor between energy units [eV] and
[J] ) . The radiation dose obtained at time
t , at a distance r from the radioactive source,
will therefore be:
D
= G. (A. <E> .1,6.10 -19 )
/ (4p r 2 ) . t ,
which is usually expressed in abbreviated form D = G . A / r 2 . t, using the constant G = <E> .1,6.10 -19/4p (for a given
radionuclide).
The radiation dose D
from the external source of radioactive radiation is given by a
simple relation *)
D = G .
A/r 2 .
t ,
where A is the activity of the emitter, r is the
distance from the emitter, t is the exposure time. The
coefficient G is the so-called dose constant
( gamma-constant ), indicating the dose rate [Gy.s -1 ] at a distance of 1
m from a radioactive source with an activity of 1Bq.
*) We mean photon
radiation here(gamma) and spot (or small enough)
emitter, placed in vacuum (or in air), without shielding
materials. It is problematic to use this relationship for
radiation a and b , because part of such radiation is already absorbed
in the source itself and further absorption occurs in air or
another environment lying between the source and the measured
location. We do not consider the half-life of a radionuclide
source here - we mean a situation where the exposure time t
is short compared to the half-life (otherwise
time integration would be necessary, similar to the following
paragraph for distributed radioactivity) .
The G- constant
has the base unit [Gy.m 2 .Bq -1 .s -1 ], but in practice it is most often used [mGy.m 2 .GBq -1 .h -1 ] - dose rate [mGy /
hour] at a distance of 1m from a radioactive source with an
activity of 1GBq. The dose G constant includes the properties of the radionuclide -
the number of photons emitted for decay and their energy, in
relation to the absorption in the irradiated substance (in water
or soft tissue); has different individual values ??for each
radionuclide. In commonly used units [mGy.m 2 /GBq.hr], the dose gamma constant for some of the most
commonly used radionuclides has the values :
Radionuclide: | positron radionuclides 18 F, 15 O, 11 C |
60 Co | 99m Tc | 131 I | 137 Cs | 192 Ir | 226 Ra | 241 Am |
G -constant: [mGy.m 2 .GBq -1 .h -1 ] |
0.138 | 0.308 | 0.016 | 0.052 | 0.077 | 0.109 | 0.201 | 3.8.10 -3 |
In practice, in order to determine
the dose from radionuclide emitters, it is necessary to take into
account the effects of radiation absorption in the
source itself or its packaging, as well as in the environment
between the source and the measured site - the resulting dose
will be lower : I = G. A / 4 p r 2 . e -m . r , where m is the linear
absorption coefficient of the medium. Photon radiation energy ® radiation dose
The energy of incident gamma or X
photons is decisive for the ways of interaction with a substance (§1.6, part " Interaction of gamma radiation and X ") and thus also for the
received radiation dose, which is caused mainly by the absorbed
energy of the secondary electrons . Photon
radiation of higher energies has a lower absorption coefficient
(linear attenuation coefficient), but if absorption occurs, the
transmitted energy - dose - is higher. The overall trend is: higher
photon energy leads to a higher radiation dose . This
also applies to the resulting radiobiological effect
. The first ejected electrons may be high energy, but more and
more electron interactions grow into a spray of ultimately low
energy electrons. Thus, harder gamma radiation also produces a
larger number of low-energy electrons, which have a higher LET
and "more time" for the formation of radicals ® higher
radiobiological efficiency .
Internal
distribution of radioactivity
To some extent, the opposite situation to an external
"spot" sealed radioactive source is a radioactive
substance dispersed (distributed) in the
analyzed or irradiated material, eg in a tissue or organ. This
situation occurs especially in diagnostic and therapeutic
applications of radiolabelled substances - radiopharmaceuticals
- in the body, where these radioactive substances are then taken up
in individual tissues and organs, according to their pharmacokinetics
. In this case, the quantum of ionizing radiation interact
immediately and immediately
with the substance immediately for its exposure to a radioactive
atom. In principle, all emitted quantum and particles (with the
exception of neutrinos) participate in the radiation dose -
electrons and positrons, Auger electrons, gamma and X photons,
alpha particles, or and reflected daughter nuclei (§1.2, passage "Nucleus recoil
") .
The charged particles, a or b , have a short
range and give off all their energy near the place of their
origin. In the case of uniform distribution of the radionuclide
in the substance with specific (mass) activity A '[Bq / kg], the
dose rate D' in [Gy / s] from short-range radiation
D'
= A'. <E> .1,6.10-19 ,
where <E> is the mean energy of the emitted particles in
[electronVolts] per decay (coefficient
1,6.10 -19
is the conversion factor between energy units [eV] and [J]) .
E.g. for the most frequently used
therapeutic radionuclide 131 I (for thyroid therapy), the dose of uptake activity in
the focal area is g grams D = 0.109 Gy. g / MBq .h.
Assuming a
time decrease of the activity of the distributed radionuclide
according to the usual exponential law A (t) = A 0 .e - (ln2
/ T 1/2 ef ) .t with an effective half-life T 1/2 ef[s]
*), the dose rate will decrease with time according to this
dependence: D '(t) = A 0 .e - (ln2 / T 1/2 ef ) .t
. <E> .1,6.10 -19 . The total radiation dose D [Gy],
caused by the radionuclide distributed in the substance, will
then be given by the time integral from 0 to ¥ : D = 0 ò ¥ [A 0 .e - (ln2 / T 1/2 ef ) .t
. <E> .1,6.10 -19 ] dt, which gives the final result:
D = A 0 . (T1/2 ef / ln2). <E>. 1,6.10 -19
.
*) The
effective half-life T1/2ef
of the activity of a radioactive
substance is given by the physical half-life T 1/2 physical of the relevant radionuclide and in the case of the organism
also by the biological half-life T 1/2
biol excretion of the
radioactive substance from the given tissue: T 1/2 ef = 1/2 phys .T 1/2 biol ) /
(T 1/2 phys + T 1/2 biol ). For the kinetics of radionuclides in tissues and
organs, the biological half-life of excretion is usually
dominant, which is usually significantly shorter than the
half-life of the radionuclide used.
If the radioactive substance also
emits high-energy penetrating gamma radiation escaping from the
analyzed volume with distributed radioactivity, as well as in the
case of uneven distribution of the radioactive substance or its
irregular time dynamics, the situation is more complicated and
radiation doses are determined by MIRD (§5.5, part " Internal
contamination ") .
Determination of the radiation dose from radionuclides
distributed in the organism, tissues and organs is important both
for determining the radiation exposure from
diagnostic applications of radiopharmaceuticals in scintigraphy,
especially in therapeutic applications of open
radionuclides (§3.6, section " Radioisotope therapy ") .
Radiobiological
efficiency of radiation. Dose equivalent, effective dose
The basic dosimetric quantity - the absorbed dose - does not
include the immediate local distribution of energy
transferred to the substance, which can significantly affect the
specific processes of physical, chemical and especially
biological effects of ionizing radiation. Therefore, another
quantity is introduced which describes the rate of energy loss
along the path of the particle in the substance, and thus also
the rate of braking of the particle and the density of
ions formed along the path :
Linear Energy
Transfer (
LET )
represents the mean energy of a locally transferred
substance passing through a particle, based on the unit
path of the particle:
L
= D E / D x,
where D E is the energy delivered to electrons and ions
by a charged particle as it passes along the path Dx . The
basic unit of linear energy transfer would be 1J/1m [Jm -1 ], but in
practice a keV/micrometer is used (1 keV m m -1 = 1,602.10 -10 Jm -1). If the
radiation has a short range (alpha radiation), the
absorbed energy is distributed along a short path, the
linear energy transfer is high, so that the ions are very
densely distributed along the path of the particle.
Sometimes the quantity of linear ionization is
also introduced , which is the number of ion pairs
related to the unit path of the particle (eg per
micrometer of the path length). The higher the
concentration of ions along the path of the particle, the
less likely they are to recombine before they interact
with the surrounding molecules in the irradiated
substance - the more pronounced will be the chemical
effect of irradiation, for living tissue the radiobiological
effect: higher concentrations of ions and consequently
free radicals cause more severe and harder to repair DNA
damage (as will be discussed in
detail below) . Since LET describes
the local distribution of ionization at the microscopic
level, this quantity is also important for the analysis
of radiation effects at the subcellular and molecular
level - in microdosimetry
.
In terms of the
biological effects of ionizing radiation on the irradiated
substance (described below), the radiation is divided according
to the density of ionization , which it induces
in the substance during its passage :
¨ Sparsely
ionizing radiation - X, gamma, beta radiation. For beta
particles with typical energies of hundreds of keV, LET is about
0.2 keV / micrometer. When passed through water or tissue, it
forms about 100 ion pairs / 1 micrometer.
¨ Densely
ionizing radiation - alpha radiation, neutron radiation,
proton radiation *). For alpha particles with energies of 4-8
MeV, the LET in the tissue is about 100 keV / micrometer, at the
end of the path in the Bragg maximum it can locally increase up
to 300 keV / m m. It forms up to 2000 ion pairs / 1 micrometer of
tissue. Densely ionizing radiation has "more time" to
form radicals - higher radiobiological efficiency
.
*) This applies to low-energy radiation, up
to about tens of MeV. The high energy (about 100MeV), proton
radiation and and or heavy ions, but most of its travel in the substances sparsely
ionizing . Only at the end of the path, in the region of
the Bragg peak , is the ionization density high
- see Fig.1.6.1 in §1.6 " Ionizing radiation ".
As the biological efficiency of different
types of radiation can vary considerably (depending on the
ionization density), for the purposes of radiobiology and
radiation protection, a so-called quality factor
Q * is introduced for each type of radiation , which indicates
how many times a given type of radiation is more
biologically effective than photon radiation - X or gamma (based
on X-rays with an energy of 200keV) .
*) Also called " radiation
weighting factor " wR or in
radiotherapy " relative biological effectiveness
" RBE (Relative Biological Effectivenes).
The value of this empirical
quality factor Q depends on the type and energy
of radiation. For X, gamma and beta radiation, the quality factor
Q = 1 , for neutrons Q » 2-5
(slow neutrons with energy up to 10keV, or again for very fast
neutrons with energy> 20MeV), 10-20 (fast
neutrons 100keV-20MeV ), for Q protons » 5
, for alpha radiation is even Q » 20
(as well as for heavy nuclei and fission
products) .
For a more objective assessment of the
effect of radiation, a "corrected" dose quantity is
introduced with the help of quality factor Q in the field of
radiobiology and radiation protection, which already takes into
account the different biological efficiency of individual types
of radiation :
The dose
equivalent (equivalent dose) in the tissue under
consideration is given by the product of the absorbed
dose D at the given site and the quality factor Q:
H
= Q. D.
The unit of dose equivalent is 1 Sievert
[Sv] *). Dose 1 S of any radiation has the same
biological effects as a dose of 1 Gy X-ray or gamma
radiation (for which the quality factor is set at 1).
Dose equivalent is a biophysical dosimetric quantity
that combines the physical quantity radiation dose
with a given type of radiation and an
empirically determined measure of its effect on
living tissue - compared to photon radiation.
*) The unit was named in honor of
the Swedish radiologist R.M.Sievert, who in the years
1920-40 studied the effect of ionizing radiation on
living tissue, laid the foundations of radiation
protection and therapeutic use of radiation. The older
unit of equivalent dose was 1 rem = 10 -2 Sv (abbreviation r
entgen e quivalent m an
- equivalent of biological damage to human tissue). This
unit dates from the 1950s and 1960s, when the
above-mentioned X-ray unit was used for
radiation exposure . The relationship between
"R" and "REM" is also by means of the
radiation quality factor Q.
As with the
dose, the equivalent dose rate (dose equivalent
rate) is introduced here as the dose equivalent increment
per unit time - the unit is Sievert per second [Sv.s -1 ].
For radiation monitoring of
individuals, the personal dose equivalent
H p
(d) is used, which is the dose equivalent at a given
location below the body surface at a depth d
in soft tissue. It is obtained by recalculating the dose
on a dosimeter using the quality factor Q and the
absorption in the tissue according to the radiation
energy.
Different tissues and organs in the body are differently sensitive to radiation and their radiation damage leads to differently serious consequences for the whole organism. Based on statistical analyzes, the own coefficients of risk of radiation damage are empirically introduced for each organ and tissue . Using these coefficients, we can then determine - estimate - the risk of damage to the body resulting from exposure to ionizing radiation. For the purposes of radiation protection, the following quantity is therefore introduced :
Tissue (organ) | bone marrow | intestine | lung | stomach | gonads | bladder | liver | esophagus | thyroid | skin | bones | brain | S -other |
w T | 0.12 | 0.12 | 0.12 | 0.12 | 0.077 | 0.04 | 0.04 | 0.04 | 0.04 | 0.01 | 0.01 | 0.01 | 0.12 |
Thus, the effective
dose D ef is calculated using the contributions of the
equivalent organ doses H T of all individual irradiated tissues: when added up, each
organ equivalent dose H T is multiplied by its tissue weighting factor w T , which expresses the
contribution of that particular organ or tissue damage to whole
body damage caused by the effects of uniform whole body
irradiation. With the aid of an effective dose of H E , the effects of
irradiating any tissue, organ or part of the body can be
converted into comparable effects resulting from uniform
irradiation of the whole body. The advantage of an effective dose
is that it makes it possible to express the radiation
exposure by a single number(the unit is again Sievert
[Sv]) even in the case of uneven irradiation, or irradiation of
only certain organs, as if it were a radiation load in the case
of uniform irradiation. This makes it possible to compare
the radiation loads of people from various sources - eg
from natural radiation, X-ray examinations, or from different
types of radiopharmaceuticals in nuclear medicine. All of these
assessments relate to the stochastic effects of
radiation - and are only very approximate " qualified
estimates ", often of a hypothetical nature
, especially in the low dose range around 0.1Gy (discussed below in the section " Very low dose issues - are harmful or
beneficial ? ") ...
Effective dose D ef it is
therefore a quantity that assesses the degree of health
risk that arises for a person from the radiation to
which he was exposed. It is an empirical biophysical
quantity that is not directly measurable
- is obtained from the measured radiation dose of a given type of
radiation by taking into account the biological effects of this
radiation and the sensitivity of the individual affected tissues
and organs. It takes into account the fact that different types
of radiation have different biological activities and that
different tissues and organs are differently sensitive, and their
damage has different health consequences for the organism.
However, it should be borne in mind that the concept of an
effective dose is only a very rough and simplified averaged
estimate of the complex and individually dependent processes of
the biological effects of radiation in organisms. It has the
character of a " qualified estimate
" of radiation doses with a number of uncertainties and inaccuracies
of the order of tens of %!
The probability of
biological stochastic effects is proportional to the absorbed
radiation dose [mGy] and irradiated area size [cm 3 ]. In planar X-ray
diagnostics, this is quantified by the quantity DAP
( Dose Area Product ) [mGy.cm 2 ], which is the product of the absorbed dose D
and the area S of the irradiated area: DLP = D. S. In
X-ray CT diagnostics, this is quantified by the DLP
( Dose Length Product ) [mGy.cm], which is the product
of the absorbed dose D and the length L of the
irradiated area: DLP = D. L. The effective dose
D ef [mSv]
for a patient, expressing the effects of radiation on the
organism as a whole, is then calculated as the product of: D ef= E DAP . DAP, or D ef = E DLP . DLP, where the
coefficients E DAP or E DLP include the averaged tissue (organ) weighting
factors w T for structures in the irradiated area (§5.7 " Radiation load in radiation diagnosis and therapy ").
To
assess the long-term effects of radiation from internal
contamination with a radioactive substance - radiotoxicity
- the so-called dose schedule is also introduced., which is the total absorbed dose of
ionizing radiation caused by a given radioactive substance in an
organism, organ or tissue over a period of 50 years from its
uptake into the organism. Radiotoxicity depends not only on the
physical parameters of the radionuclide (half-life, type and
energy of radiation), but also on the chemical characteristics of
the contaminant, which determine the metabolism, distribution to
the various authori n s,
half-life, route of excretion (see below §5.5, section " Internal
contamination ") -
the residence time of a radioactive substance in tissues and
organs.
Collective
is sometimes used to
evaluate the exposure of selected groups of people or populations
equivalent or effective dose, which
is the sum of the respective doses of all individuals in a given
group. These data can be used for demographic radiohygienic
analyzes and to optimize radiation protection.
Physical and
biophysical dosimetric quantities
It is necessary to draw attention to the different nature of
individual dosimetric quantities. Dose, kerma, exposure, linear
energy transfer and some others are physical
dosimetric quantities that
can be (at least in principle) determined on the basis of purely
physical measurements. They describe the objective
measure of the physical (and
possibly induced chemical) effect of radiation on substances.
They can be used not only in biological, but also in various
other technological applications of radiation, where they
determine the degree of required (or undesirable) effects of
radiation on a given material or process. The field of biological
and medical applications is the dominant field of application of all dosimetric quantities.
Dose equivalent and effective dose (and
other quantities derived therefrom) are the biophysical
dosimetric quantity
intended for radiobiology and radiation protection
- basic physical quantities
generated by calculation using empirical physical
and biological factors -
quality factor Q and tissue weighting factors w T . They
are not directly measurable. Approximate values of conversion
factors were determined by radiobiological experiments
and based on the results of randomized
clinical trials . It is
necessary to further distinguish which quantities relate to
stochastic and deterministic radiation effects.
Methods for dosimetric
determination of radiation doses
The doses of ionizing radiation are determined by the physical
methods described in detail in Chapter 2 " Detection
and spectrometry of ionizing radiation
". Dosimeters are used , which are simple
radiometers - ionization chambers, GM detectors, scintillation
detectors, film dosimeters, thermoluminescence and OSL dosimeters
- calibrated in dosimetric quantities: radiation
dose [mGy] or [mSv], dose rate [mGy / s] or [ mSv / s].
Dosimeters are used to perform physical measurements (often using phantoms modeling the tissue
environment and geometric configuration of irradiation) , monitoring workers and patients ("in
vivo" personal dosimetry), radiation
monitoring of work and environment.
Biodosimetry
Sometimes there are situations where radiation exposure (or
exposure is suspected) without the relevant persons being
dosimetrically monitored - it is irradiation with an
unknown dose . When physical dosimetry is lacking, the
possibility of retrospective dose determination
(or its estimation) arises by monitoring changes in some
biological parameters. Biological dosimetry or biodosimetry
is a radiobiological method that helps determine the size of the
absorbed dose according to the type and intensity of the post- radiation
response of the
organism (these radiobiological effects are discussed in detail
in the following §5.2 " Biological
effects of ionizing radiation".
Biological parameters such as changes in blood counts
, occurrence of chromosomal aberrations or
micronuclei in blood cells, observation of somatic mutations in
blood cells, DNA or mRNA damage, increase in p53 protein
concentration, ATM-kinase, ....... can be used for dose
reconstruction . As adequate treatment needs to be started as
early as 1-2 days after irradiation, it is desirable to use expression
biochemical analysis (statim), such as ELISA or RT-PCR. ...
5.2.
Biological effects of ionizing radiation
As mentioned above, the primary effect of ionizing radiation on
matter is the interaction of the quanta (electromagnetic
or corpuscular) of this radiation with the
electron shell of atoms, occasionally with atomic nuclei. The
result is excitation and ionization of atoms ,
which can lead to physical changes and chemical reactions
, and in the case of living tissue to biochemical changes
. These secondary effects can then lead to changes and damage to
the irradiated organism, or even to its extinction - death.
The basic building blocks of all
living tissues are cells . Therefore, in order
to understand the biological effects of ionizing radiation, the
mechanisms of action of radiation on cellular and subcellular level . This
is related to the chemical and biochemical effects of ionizing
radiation at the molecular level . Therefore, we
will analyze these aspects first, followed by an analysis of
radiation effects at the level of tissues , organs
and the whole organism .
Note: However,
these molecular, cellular and tissue aspects cannot always be
strictly separated, so they will sometimes overlap when
interpreted.
From a biological and medical point
of view, the special field of radiobiology deals
with the effects of radiation on living tissue and organisms . We
will not deal with the details of this field here, they are
mostly outside the scope of our physical treatise. We will
mention here only those findings that are important from a
physical point of view , for applications of
radiation in medicine and biology and also from the point of view
of radiation protection methods .
Cells
- basic units of living organisms
All living organisms are formed by cells
*) - small formations or "chambers" bounded by the cell
wall ( cytoplasmic membrane - lipoprotein with 2 layers
of phospholipids) and filled with viscous aqueous colloidal
solution of various chemicals, especially complex organic
macromolecules. The field of biology, studying cells, their
structure and function, is called cytology (Greek cytosus = cavity ) .
*) R. Hooke first observed cork cells as early as 1665
using a simple microscope, other cells were more perfectly
observed by A. Leeuwenhoek. Name of the cell
(lat. Cellula ; cella = chamber)
arose from the resemblance to cells in honeycomb honeycombs.
JEPurkynì also made a significant contribution to the origin of
the science of cells - cytology . Only the discovery
of cells and the gradual recognition of complex biochemical
reactions taking place in cells at the molecular level
transformed at the end of the 19th and in the 20th century.
biology and medicine from descriptive empirical doctrine
(description of species, "counting of petals and
stamens", external manifestations of diseases, ..., with
many unsubstantiated and erroneous assumptions) to real science
, enabling to understand the essence and functioning of
life on a uniform exact basis , for physiological and
pathological situations. Research into complex biochemical
processes at the subcellular level will continue for a long time.
Viruses
On the border between living organisms and
inanimate nature, there are viruses (Latin virus
= poison ) - intracellular parasites of microscopic
dimensions of about a hundredth to a tenth of a micrometer. They
consist of nucleic acid (DNA or RNA), encased in a protein shell
( capsid ). Although viruses contain nucleic acids that
carry genetic information in their sequence, they are unable to
grow and produce their own proteins, reproduce, or obtain and
store nutrients and energy - they need a "host" cell to
do so. When a virus enters a cell, it parasitizes on it, uses its
nutrients and can kill it. Or it can copy its genetic information
into the cell's DNA (via reverse transcriptase- see
below) and force ("reprogram") the host cell to work in
favor of the virus. In higher organisms, viral infections are the
cause of many diseases.
Proteins - the basic building
blocks and functional substances of cells
In the basic filling of the cell, called the cytoplasm (Greek cytos = cavity, plasma = creation )
, more complex structures - organelles -
"float" . The liquid part of the cytoplasm, which is an
aqueous gel of large and small molecules, is called the cytosol
. The cytoplasm is composed mainly of a colloidal solution of
protein or proteins (Gr.
Protos = first , they are biological substances
primordial importance), - polypeptide chains are linear
polymers of amino acids . Amino
acids are molecules containing a carboxyl group
(-COOH) and a nitrogen amine group (-NH 2
); these groups and other atoms (hydrogen atom and
side chain) are attached to the central and to the
carcass . Amino acids are able to combine with each other by
a so-called peptide bond , in which the carboxyl
group of one amino acid reacts with the amino group of another
amino acid. Thus, even considerably long polypeptide chains
of e- proteins can be formed - polymerized
. Of the large number of chemically existing amino acids, only
occurs in their cells 24 species (20
basic, 4 special ...).
The carboxyl
and amine groups, the hydrogen atom and the side chain are
attached asymmetrically (with the
exception of glycine) on the central (alpha) carbon - chiral
asymmetry , which manifests itself in the ability to twist
the plane of polarized light. Depending on the spatial
orientation of the attached groups on the alpha-carbon, the amino
acids can be levorotatory " L
" or dextrorotatory " D
" (from Latin Leavus = left , Dexter
= right ) . Polypeptide bonds can only occur between
amino acids of the same chirality, L or D. In the early
stages of prebiotic evolution, the "left-handed"
chirality of amino acids randomly prevailed, and this preference
then evolved to all biochemical processes. Thus, only levorotatory
alpha-L-amino acids are present in biochemistry ; and
natural carbohydrates are in turn D-dextrorotatory ...
The primary structure of proteins is
given by the order of amino acids in the
polypeptide chain ( peptide bond
represents the CN connection between two amino acids, leading to
the presence of the peptide group -CONH-) . There
are 20 types of amino acids in proteins, both aliphatic (alanine, glycine, leucine, valine, ...) and aromatic
(with benzene nucleus - phenylalanine, tyrosine,
tryptophan, ...) , acidic (aspartic
acid, glutamic acid) , basic (lysine,
histidine, arginine) , with bound sulfur (cysteine, methionine) and several others.
Individual amino acids have different biochemical properties, so amino
acid sequencesin the protein it determines the chemical
properties of the protein and its spatial structure. Linear
polypeptide chains are formed into a spatial (3D) structure due
to the formation of hydrogen bonds between the groups of the
protein backbone - the secondary structure is either regular
repetitive (helical, bending and fiber folding), or irregular and
compact, or. more complex joining of different fibers and
sequences (tertiary structure). Some types of proteins are the
basic building blocks of cells, other types of
proteins perform specific functions through
their complex chemical reactions.cells and tissues (as will be
specifically mentioned below in a number of places below). The
set of proteins that are contained in the cell or that the cell
can synthesize, defines its ability to perform various
biochemical reactions - processing (decomposition and synthesis)
of chemicals, obtaining chemical energy, creating building
"materials" of cells and other parts of the body -
measures of the resulting properties of cells and organisms. A relatively new
scientific discipline called proteomics deals
with the systematic study of proteins - their origin, structure,
interactions and functions in cells and organisms . The
functional properties of some proteins are discussed below in the
section " Proteins, enzymes,
kinases ".
Biochemical reactions - the basis of
cell life
Chemical reactions in cells are controlled and highly organized
, with a complex DNA molecule ( deoxyribonucleic
acid , see below) playing a fundamental controlling role ,
which encodes the composition of proteins - their primary
structure, the order of amino acids. Cells have the ability to
metabolize, grow, and make their own "copies" by
dividing one cell into two (for asymmetric
division into stem and effector cells, see below) . The
simplest forms of life, single-celled organisms , are
made up of separate cells. Higher multicellular organisms
are formed by a community of a large number of cells, usually differentiated,
where different cells perform their different specific functions,
coordinated by chemical regulatory mechanisms and
"communication systems".
Biochemical reactions usually
involve highly complex organic molecules containing large numbers
of carbon, hydrogen, oxygen, nitrogen, phosphorus and others. The
molecular weight of these macromolecules
in biochemistry and molecular biology is expressed in special
units called kilodaltons (kDa), which is 1000
Daltons (Da). 1 Dalton corresponds to 1/12 of the mass of a
carbon atom, ie roughly the mass of a hydrogen atom, 1Da =
1.66.10 -27 kg (J.
Dalton was an English chemist, lived in the years 1766-1844,
significantly contributed to the knowledge of the laws of atoms
and their chemical merging). Thus carbon has 12Da, methane
CH 4 has a mass of 16Da, water
has 18Da, glucose C 6 H 12 O 6
has 180Da; the p53 protein has a molecular weight of 53 kDa.
The difficulty of
understanding the function of living organisms
Despite all the advances in biochemistry and molecular biology,
our understanding of how living organisms work at the molecular
level is still very limited. The number, complexity, and
interconnectedness of the biochemical processes that take place
in living cells still defy our ability to comprehensively analyze
and understand the mechanisms of the dynamic
behavior of these systems. In addition to the
extent and complexity, stochastic effects are
also applied to intracellular systems caused by random movements
of molecules. Some biochemical substances are contained in cells
only in very small concentrations, sometimes only units or tens
of molecules. With such a small amount, collisions and reactions
of these molecules occur relatively rarely, and thus with
considerable statistical fluctuations. Such random (stochastic)
phenomena can have a significant effect on the dynamics of
biochemical processes, which can be reflected in the behavior of
the whole cell.
Prokaryotic
and eukaryotic cells
Such a complex phenomenon as life has undergone a very long and
complicated development , a number of stages of
which we do not yet know (for the evolution of
life, see the work " Anthropic Principle or Cosmic
God ", passage " Origin and evolution of life "). In terms of structure and development,
cells can be divided into two basic groups :
Prokaryote
(Greek: pro = anterior, karyon =
nucleus , cells without nucleus, "pre-nuclear")
, whose circular DNA is exposed and floats freely in the
cytoplasm in a nucleus called a nucleotide.
. Prokaryotes are the primitive oldest developmental form of
cells, now occurring as bacteria and cyanobacteria
. We recognize two groups of bacteria: eubacteria ,
which occur in large numbers in our environment; archaebacteria
, living in an environment inhospitable to other organisms (hot
springs, seabed, acidic or alkaline environment). The dimensions
of the bacteria range from about 1-10 m
m. These evolutionarily very old
cell types form single-celled organisms , they do not
form any functionally differentiated tissues, they can only
associate into colonies .
Eukaryotes (Greek eu = normal, correct, karyon = nucleus -
ie "true nuclear") , whose DNA (linear, spiral
shape) is concentrated mainly in the cell nucleus
, where it is associated with histones in chromosomes ,
which are multiple and contain other chromosomal proteins.
Respiratory and metabolic enzymes are concentrated in organelles,
particularly mitochondria and lysosomes (see
below). These cells also have a so-called cytoskeleton -
a system of flexible fibers (formed by microfilaments
and thin hollow tubes - microtubules ) in the
protoplasm, providing mechanical support to the cell structures;
they also mediate the intracellular transfer of complex molecules
between the nucleus and other organelles (they then form a mitotic
spindle during cell division ). Eukaryotic cells have
relatively larger dimensions, about 5-100 m
m. In addition to unicellular organisms, they form organized
communities of multicellular organisms with cells
functionally specialized in tissues and organs ,
including humans. In the following text, we will consider only
eukaryotic cells, especially somatic cells cells
incorporated into tissues and organs; prokaryotic cells will be
briefly mentioned in several places for comparison. The figure
shows only a very simplified scheme of cell structure, with
enlarged sections of the cell wall (cytoplasmic membrane),
cycloskeleton (microtubule), nucleus (histone-borne DNA) and DNA
structure (some nucleotides).
Eukaryotic cell structure. Details of
some structures are schematically drawn in enlarged sections
(frames).
DNA, RNA, proteins,
chromosomes, telomeres
The whole mechanism of cell life
organization is based on a cooperating system of nucleic
acids DNA (deoxyribonucleic acid ), RNA
(ribonucleic acid ) and proteins
: genetic information is stored in DNA, which is transcribed into
RNA, which then serves as matrices for protein production.
Different types of proteins are not only the basic building
blocks in cells and tissues, but are also carriers of
cell and tissue function ( enzymes ).
The essence of life: |
From a chemical point of view, life is a very complex system of molecules that can organize itself , metabolize using chemical binding energy, grow , reproduce and develop over longer periods of time . |
Deoxyribonucleic
acid DNA
- deoxyribonucleic acid ;
a weak acid reaction is caused by
phosphoric acid H 3 PO 4 bound in nucleotides . It is a very complex long
macromolecule , a polymer of repeating sequences of
deoxyribonucleotides, which has the shape of a double spiral in
eukaryotic cells - Fig. 5.2.2a. DNA contains about 100,000 ¸ 200,000,000 nucleotide pairs,
has a molecular weight of about 2 ¸
100MDa (megadaltons) (lower limit is for DNA
plastids, mitochondria and prokaryotic cells, upper limit for
human DNA). The developed DNA would have a linear length
of decimetres to meters (in humans about 2m ..!
..) ; in cells, however, it is very compactly coiled in chromosomes
only a few micrometers in length (see below)
.
From a chemical
point of view, DNA has a polymeric structure - it consists of a chain
of repeating and interconnected similar building blocks
called nucleotides , which are formed by phosphate
H 3 PO 4
(phosphoric acid binding part), deoxyribose
(5-carbon sugar, pentose - monosaccharide 2- deoxy- b- D-ribose (hence the name DNA), purine and
pyrimidine bases (nitrogen heterocyclic
compounds). Nucleotides differ representation 4 different bases:
adenine A , guanine (a purine base) G , cytosine C
, thymine (pyrimidine base) T . These four types of
nucleotides are arranged in DNA in a certain order or sequence
. This unique grouping of nucleotides in a strand is the basis of
hereditary information stored in the DNA - the genetic
code . They form triplets, each encoding
one amino acid . DNA thus contains information
about the structure of proteins composed of
these amino acids.
The section of a DNA molecule that
encodes the order of nucleotides in a particular functional RNA
and subsequently, through mRNA, also determines the order of
amino acids in a particular protein with a specific function,
"produced" by a cell, is called a gene
(Greek: genos = genus, origin; talent ) *) . Thus, genes provide "instructions"
for protein production - see below " Ribonucleic acid -
proteosynthesis ". Although some genes are transcribed
into RNA, it does not go further into proteins; the resulting
ribonucleic acids have some regulatory functions. Overall,
however, in eukaryotic cells, only a small fraction of DNA
sequences encode any (functional) proteins. It is just over
20,000 genes, which represents only about 5% of the human genome.
Most DNA sequences are sort of ""-" waste
"or" unnecessary "DNA ( junk DNA, noncoding
DNA ), which is a relic of a complex path of evolution
(fossil sequence -" old junk "). They were often
originally" parasitic "genes of viral origin, which
were incorporated into DNA Some of them have been transformed and
functionally involved, most have remained dysfunctional, others
can potentially endanger the organism (possibly
interacting in the formation of tumors ..? ..) However , this " unnecessary DNA " is
also in many cases transcribed into RNA, which is a (protein)
non-coding but has a regulatory function - it
determines, for example, the start, stop or intensity of
transcription of coding parts of DNA.unnecessary "( junk),
Is now focused extensive project ENCODE ( Encyclopedia of DNA Elements Code ; besides
Eng. Encode = encode ) launched in
2003.
*) Genes,
genetics
Inheritance
- the transmission of some properties of living organisms to
offspring, between generations - has been observed for a long
time. Some biologists (such as J.G.Mendel in the 1960s in several
years of trying to grow peas with different colors of flowers)
empirically traced some patterns of this inheritance, but its
true biological cause remained unknown for a long time. Only the
development of fluid molecular biochemistry in
the middle of the 20th century. showed that the essence of
hereditary information is a DNA molecule .
Another structural peculiarity of
genes in eukaryotic DNAs is that the functionally coding
sequences of deoxyribonucleotides - called exons (Greek exo = outer unit) are interrupted
by non-coding sequences, so-called introns (lat. Intro = inner unit) without
genetic content, whose role, probably regulatory, has not yet
been fully clarified. Shortly after transcription into mRNA are
intronic sequences "cut" (ie. Splicing ) and
thus excluded from the further process of gene expression; the
subsequent joining of the coding sequences (derived from exons)
creates a functional mRNA, allowing the continuous synthesis of
polypeptide chains of proteins during translation.
To imagine genetic information only
linearly as a long line of nucleotides - the "letters"
of the genetic code - is simplified and can be misleading;
geometric dimensions also apply. The double helix of DNA is
intricately twisted and intertwined, so that parts of DNA that
are separated by a long series of nucleotides can come into close
proximity in the nucleus and then influence each other's genetic
activity.
When a cell divides, DNA nucleotide
sequences are able to make their own exact copies
, which pass on genetic information to future generations. A
specific form of a gene for a learned trait or property of an
organism is called an allele (Greek:
allos = other ) , eg a gene for flower color. If
a given organism has the same alleles in its gene pair, it is
referred to ashomozygous , heterozygous for
different alleles .
The structure of DNA
DNA is made up of two parallel strands (also called strands
), connected by hydrogen bonds between the nuclear bases into a
kind of "ladder" that twists into a double helix. Both
chains are complementary to each other , their
bases are precisely paired with hydrogen bonds. The nucleotide
sequence on one strand is fully determined by the sequence on the
other strand ("positive-negative" pair). These hydrogen
bonds between complementary bases cause double-stranded DNA,
despite its complexity, to be a very stable macromolecule
. Only two nucleotide pairs always pair with each other: C « G
, A « T ( Watson-Circk pairing ) ;
these base pairs form a kind of "ladder step" of DNA.
Revealing the
structure of DNA
We cannot directly observe the structure
of DNA molecules, due to the very
small transverse dimensions and the compactification of the
length dimensions. Under the microscope, we observe only
virtually unstructured chromosomes. The assembly of the DNA
structure was aided by X-ray diffraction crystallography
(it is described in more detail in §3.3, section " X-ray
diffraction analysis of the crystal lattice structure
"). It was possible to grow small DNA single
crystals , which reflected it diffractively when
irradiated with X-rays, which created interference
patterns on the photographic medium., which made it
possible to determine the distribution of atoms
in the molecule. A team of researchers R. Franklin, R. Goling, F.
Crick and J. Watson at the MRC Molecular Biology Laboratory in
Cambridge in 1953 completed the analysis of DNA structure and
Crick and Watson created a model that very
successfully explains all cellular genetic processes.
This structure
allows replication : for each of the strings it
is possible to create a new string, completely identical to the
original. During replication, the two strands of DNA move away
from each other, and a new second strand is added to each of
them, nucleotide by nucleotide. Each of the two newly formed DNA
molecules has one strand from the original molecule and the other
newly synthesized. During cell division, DNA is thus able to
accurately reproduce itselfand thereby transmit
genetic information to future generations of cells. Replication
is a very precise process in which control and correction
mechanisms are built . Each time a new nucleotide is
added to a new DNA strand, the correct pairing of the previous
nucleotide is checked; if the pairing is not correct, the repair
enzymes immediately remove the faulty nucleotide and replace it
with the correct one. Furthermore, the correct base pairing
between the original DNA strand and the newly synthesized strand
is checked, with the mismatched nucleotide on the new strand
being replaced by the correct one. Thanks to these ongoing fixes,
the resulting replication error rate is only ~ 10 -9! Much more often
than replication failures, nucleotides and the genetic sequence
of DNA are damaged by external influences - ionizing radiation
and reactive chemicals ( genotoxic
effects discussed in detail below) . Cell division and the cell cycle are discussed below in
the section " Effect of radiation on cells ", section " Radiation effects during the
cell cycle ".
Telomeres
Both end parts of DNA of eukaryotic cells are provided with
so-called telomeres ( Greek
telos = end, meros = part ) - marginal
"termination" complexes of repeating sequences, which protect
the ends of chromosomes from unwanted chemical bonds *), as well
as from the "false" evaluation of the end part as a DNA
break (and the initiation of repair mechanisms or apoptosis - see
below). Telomeres have a constant structure of repeating
sequences, very similar in different biological species. In human
and most other eukaryotic cells, it is a short hexanucleotide
sequence [TTAGGG] n of up to n = 2000 repeats.
*) It can be compared to a metal or plastic
reinforcing end of shoelaces, which protects them against
fraying.
A complex nucleonprotein complex with a specific
function is bound to telomeres. One of the studied proteins of
this kind is TRF1 (Telomeric Repeat-binding Factor 1 ),
which binds to the ends of the telomere and prevents
telomerase (see below) in its activity to synthesize the
shortening ends of the telomere. However, there is the enzyme tankyrase
, which removes the TRF1 protein and thus helps telomerase to
work.
However, most common
replications do not completely synthesize telomere-containing DNA
ends - telomere shortening occurs. The enzyme
DNA polymerase, which replicates the DNA sequence, is not able to
copy it completely to the end regions. With each mitotic division
of the cell, the length of the telomeres is shortened by about
50-150 bases, leading to a gradual reduction in the protection of
the DNA ends; eventually this results in a loss of mitotic
ability of the cells. With excessive truncation, telomeres no
longer adequately protect the ends of chromosomes, which cellular
control mechanisms evaluate and arrest the cell cycle (such cells
remain in the G1 phase of the cell cycle or undergo apoptosis).
Mitotic shortening of telomeres in DNA is
the main mechanism of the process of "aging" of cells,
called senescence *) - see
also below " Extinction -
death - of cells " . Telomere shortening acts as a "mitotic
counter" - eukaryotic cells can only reach a certain limit
in the number of their divisions, the so-called Hayflick
limit (about 50-80 cycles); then they lose the
ability to divide, replicative aging
(senescence) of cells occurs. However, prokaryotic cells that
have circularly ordered DNA without telomeres can divide
indefinitely.
*) Cell aging is probably multifactorial
a process involving both intracellular "program"
molecular mechanisms and time-accumulating exogenous detrimental
factors affecting cell viability. Progressive damage to cells by
reactive forms of oxygen and nitrogen (radicals) during
metabolism and tissue life is applied, with the ever-decreasing
capacity of antioxidant mechanisms. Note :
Occasionally there is speculation about evolutionary
significance
shortening of telomeres, replicative aging
and extinction of organisms: that this process prevents the
overfilling of limited living space by long-lived organisms,
which would slow down evolution. However, this hypothesis is
somewhat debatable for two reasons. First, replication truncation
of telomeres is only one of the mechanisms of senescence, but
most importantly the environment has been (and still is) filled
with a huge number of prokaryotic organisms with circularly
ordered DNA without telomeres, where this effect does not apply;
and yet the evolution of eukaryotes has continued successfully
... In interspecies competition and evolution of eukaryotes,
however, it may have some significance ..? ..
However, there is a
special enzyme called telomerase (it is a complex composed of RNA and proteins: RNA
matrix serves as a template for sequence synthesis). telomere and
DNA, reverse transcriptase transcribes from RNA to
DNA) , which is able to synthesize
the terminal sequences of telomeres and thus prevent
their shortening during cell division. For the successful
functioning of telomerase, the above-mentioned enzyme tankyrase
is required , which causes inhibition of the telomere-bound
protein TRF1 ("synergistic" action of telomerase and
tankyrase). Such cells are then capable of unrestricted
division ( immortilization -
"immortality" of cells), which physiologically takes
place only in the early stages of development of the organism in
dividing embryonic cells and then only in
undifferentiated stem cells; pathologically applied in cancer
cells(§3.6 " Radiotherapy ", passage " Carcinogenesis ").
However, some new experiments show that telomerase is not the
only mechanism for DNA telomere recovery. An alternative method
of "treating" telomeres may be telomerase-independent
inter-telomeric homologous recombination (see " Reparation
Processes " below) , which may lead to elongation of telomere segments,
sometimes several-fold. This method is observed in some plants
and is possibly evolutionarily older than telomerase. Closed
structures, a kind of "telomere loop" at the ends of
the DNA, which can replicate or elongate (mechanisms
of a kind of "rolling circle") have
also been observed .cells performing specialized activity in
tissues and organs lose the ability to divide indefinitely and no
longer divide after reaching the Hayflick limit.
Note: Mitotic
telomere shortening occurs only in eukaryotic cells with linearly
ordered DNA, where the polymerase is unable to ensure complete
replication of the terminal portions. For prokaryotic cells
(bacteria) with circularly arranged DNA without telomeres, the
limit on the number of divisions does not apply.
Chromosomes
There are two types of DNA in eukaryotic cells: nuclear
and mitochondrial (this is mentioned below in the
section on mitochondria). Nuclear DNA is located in the cell
nucleus in chromosomes (Greek chromos =
color, soma = body) - specific structures about 2-5 mm long, after staining
(with classical Giemsa-Romanowski dyes or fluorescent dyes)
observed in an optical microscope. Chromosomes are composed of
protein carriers, so-called histones (they are small
basic nucleoproteins with a high content of positively charged
amino acids, forming complexes with DNA), around which the DNA
molecule is "wrapped". The chromosomes in cells are
arranged in sets , with the number of chromosomes in one
set (so-called monoploid number x) being normally the
same for each cell in a given organism; in humans it is x = 23
chromosomes. The number of homologous sets of chromosomes in a
cell, called ploidy, is different for different species
of organisms. In humans, most cells are diploid (2 sets
of chromosomes, 23 from the mother and 23 from the father), but germ
cells are haploid (only one set of 23 chromosomes). A
higher number of chromosome sets than 2 is referred to as polyploidy
(triploidy-3, tetraploidy-4, hexaploidy-6, ...); often found in
plants, probably played an important role in evolution. Another
anomaly is the so-called aneuploidy , when a particular
chromosome can be multiplied 3 × or 4 ×, or reduced - 1 ×, or
completely lost. Anomalies in the number or structure of
chromosomes, so-called chromosome aberrations , arise as
a result of disorders in mitosis and DNA damage (see below).
Ribonucleic acid RNA
Another important
"informational" macromolecule in cells is ribonucleic
acid RNA. It is somewhat simpler than DNA, with which it
is similar in many respects: RNA is also made up of a
sugar-phosphate polynucleotide strand , which,
however, contains the monosaccharide ribose
instead of deoxyribose . RNA further differs from DNA in that the
pyrimidine base uracyl U occurs
instead of thymidine T. (similar to thymine,
uracyl forms a complementary pair UA with adenine). The other
bases adenine, guanine, cytosine, are the same in both nucleic
acids.
"The World of RNA
"
In terms of genetic information in current cells, RNA plays a
"helper" role, although necessary (see below). However,
evolutionary biology concluded that early life was probably based
on RNA (the " RNA world "),
the first simpler molecules of which could have arisen
spontaneously from prebiotic molecules. The original precursors
of the present cells - protocells - were probably just
"clumps" of ribose molecules, polymerized into short
stretches of RNA, coated with water into a simple phospholipid
membrane. Under appropriate conditions, RNA molecules are able to
make copies of themselves and thus "multiply". Peptides
(" RNA-peptide world ") may have aided these
processes . Suitable combinations of peptides can produce enzymes
Replicating RNA molecules encoded properties that were
"genetically" passed on to the next generation. Mutations
that occurred by chance during "copying" led to
changes, of which the "positive" ones allowed these
early cells to adapt better to the environment and thus compete
with each other by natural selection ( Darwinian evolution
). It was only later that a suitable combination of RNA molecules
developed DNA , which, thanks to its greater
chemical stability, took on the role of primary genetic
molecule for long-term storage of genetic information
throughout the organism and for transmission to future
generations. RNA began to function as a "bridge"
between DNA and proteins (see below " Information
transfer - proteosynthesis")"). Figuratively can
be said that" mace "preservation of the genetic
information transmitted RNA's duplicate" sister "DNA
and to himself let the role of" medium "(mRNA). Thus,
initially created prokaryotic cells (without nucleus and
organelles) with cyclically arranged DNA; later evolved complex eukaryotic
cells with a linear arrangement of DNA in a form of a double
helix located in the core and with a number of organelles
fulfilling specific functions of the cell metabolism.
Information
transmission - proteosynthesis
Fundamental process whereby information contained in a DNA
transferred into a particular structure or feature is protein
synthesis or proteosynthesis. So-called
gene expression, in which the information stored in the
DNA gene is converted and realized on a specific cellular
structure or function, takes place in two stages. First, transcription
occurs (transcription, copy), when an information or mediator
RNA ( mRNA - messenger RNA ) is created , the
strand of which is a copy of the base sequence of one of the
strands of the DNA double helix *). The transcription of DNA into
RNA is catalyzed by an enzyme called DNA-dependent RNA
polymerase . The single-stranded linear mRNA molecule
separates upon transcription and travels to the cytoplasm. The
mRNA is then translated (translated, transcribed) into a
protein whose amino acid sequence is encoded by the mRNA as a
template or template; this second stage - protein synthesis -
takes place in ribosomes (see
below "Ribosomes - protein factories") . The information is thus translated from the
"language" of DNA nucleic acids into the
"language" of the amino acids from which the proteins
are assembled. The proteins formed can be used by the cell
itself, or they can travel to other cells, tissues or organs.
*) RNA
splicing
As mentioned above in the DNA section, only a small part of the
DNA sequences encode some (functional) proteins. The coding
regions of the exon represent only small
"islands", which are surrounded by a "sea" of
unnecessary intron sequences.- "genetic
litter" which makes up about 9/10 of the sequences present.
Short sections of DNA that encode proteins are interrupted by
long sequences that do not encode anything and should be removed
before proteosynthesis. Removal can take place noncoding DNA
(whose structure must be maintained as the genetic information
for the next cell generation), but it does so only at the RNA
level by a process called splicing ( splicing
) RNA. The information contained in the DNA is first transcribed
into a precursor mRNA molecule ( pre-mRNA),
which is an exact copy of a single strand of DNA; it therefore
contains many non-coding sections. During pre-mRNA splicing, the
boundaries between coding and non-coding regions are recognized
by small nuclear RNAs by base pairing. The non-coding portions
are then removed and the protein coding
sequences are recombined into the resulting mRNA
, which enters the cytoplasm (ribosomes) for proteosynthesis.
New research (the ENCODE project) has shown that non-coding RNA
derived from "genetic litter", "unnecessary
DNA", is often used to regulate the expression of coding
genes.
The so-called transfer
RNA participates in the translation process (tRNA), whose function is to transfer amino acids to the
ribosome. The three nucleotides in the mRNA that determine the
inclusion of one amino acid in a protein is called a codon
. In tRNA, it corresponds to a trio of nucleotides that bind to a
codon - the so-called anticodon , which is specific to
each type of tRNA. The transfer tRNA carries in its acceptor part
on the one hand the corresponding amino acids, on the other hand
it has a triple nucleotide (anticodon) which can pair with the
codon of the mRNA. Its molecular mechanism ensures that the
correct amino acids are included in the protein according to the
given sequence of the genetic code. In this two-step proteosynthesis
the resulting proteins then realize the appropriate structure or
function in the cell or organism. It can be said that genetic
information in a cell or organism is expressed in the form of
proteins: the genome (a set of hereditary
information) is transformed into a proteome (a
set of all the proteins in a given organism).
Note: There
is also a reverse process, so-called reverse transcription
, in which an RNA molecule is able to store its gene sequence in
DNA through the enzyme reverse transcriptase . This
occurs when cells are infected by certain viruses ,
whose RNA can thus enter the DNA of eukaryotic cells and alter
their genetic sequence. Reverse transcription into this
category in a way, the above-mentioned
synthesis of DNA telomeres by telomerase belongs .
After the synthesis
of proteins in ribosomes, their post-translational
modifications can occur - additional chemical
modifications that can give proteins new properties and regulate
their functions. Such a typical modification is phosphorylation
and dephosphorylation (attachment or detachment of the phosphate
group PO 4
to a protein), acting as a "switch" between the active
and inactive forms of the protein.
Thus, most genes encode a protein, and
these proteins perform almost all functions in the body.
Furthermore, through proteins, individual genes can interact
indirectly with each other : one gene produces a
protein that has (in addition to possibly
other functions) the
ability to alter, for example, the rate of transcription of
another gene. This creates a kind of gene regulatory
network with very complex behavior.
Proteins, enzymes,
kinases
Proteins -
proteins (Greek protos = first ;
biological substances of primary importance) - are the basic material of life. They are the building
material of various structures in cells and tissues and
the carrier or "executor" of many biochemical
functions . These biopolymers consist of amino
acids (there are 22 basic types of
amino acids) linked by chemical bonds into
long chains as "string beads" (as
detailed in the introductory passage on cells) . Not only the amino acid sequence - the primary
structure , but also the geometric spatial structure
(3D) - the secondary and tertiary structure into which
the amino acid chains are folded or "packed" is
important for the proper function of proteins . The specific (and
relatively unchanged, rigid) three-dimensional structure largely
determines the function of proteins by the " key and
lock " method.": in order for a protein to bind to
a specific target molecule or structure, as when a key fits into
a lock. The primary structure, given the amino acid sequence,
does not necessarily determine the geometric arrangement of the
protein. Special protein molecules called chaperones
(fran . chaperone chaperone = ) - are the "guardians" provide for proper
spatial structure of proteins, prevent formation of incorrect
linkages (some or chaperones. improperly
packed structure again "expand") .
Some proteins, however, are not fixedly
arranged spatially shaped, unstructured , flexible
- whether as a whole or containing parts with a fixed structure
as well as flexible parts, or they consist of a three-dimensional
shape "as needed". Such flexible proteins can bind to
various types of molecules (they are "promiscuous");
examples are p21 and p27 proteins. The known p53 protein also
contains unstructured sections.
Proteins that control or catalyze
biochemical reactions or processes are called enzymes
(the name comes from the Greek zyme =
yeast, yeast ) . Each enzyme is
"specialized" for a particular function; enzyme +
substrate ® product + enzyme. The biochemical names of enzymes are
usually formed by a base related to the function and the suffix "-ase"
or "-ase" : e.g.fats to simpler
substances), proteinase (breaks down proteins
into smaller parts, peptides ), amylase (a
digestive enzyme that breaks down long starch molecules (Greek amylon = starch ) into
simpler carbohydrates), phosphatase (an enzyme that
releases a phosphate group from its binding to another
compound).
Important enzymes are the so-called kinases
(Greek kineo = move ) , which are able to activate certain processes and
transfer phosphates to other compounds, acceptors
that have OH groups; a phosphoester is formedacceptor
molecules. The transfer and binding of the phosphate group
PO 4 (the
source of which is most often adenosine triphosphate ATP
, see "mitochondria" below) - phosphorylation
- to a certain site of a protein activates the specific reactivity
for which the phosphate group supplies energy. Protein
kinases , proteinases, and molecules that regulate their
activity, link the various signaling pathways in
the cell. MAPK(mitogen-activated
protein kinases) is a group of cellular kinases that gradually
phosphorylate with each other to form a network or cascade
leading and amplifying the signal; at the end of the pathway are
substances sensitive to phosphorylation. The pathways usually end
in the nucleus, where they phosphorylate certain transcription
factors.
The biochemical names of some kinases are formed in a
similar way to other enzymes. Tyrosine kinase is
an enzyme that transfers phosphate to the hydroxyl group of the
cyclic amino acid tyrosinebound in the protein. This
affects the function and activity of the protein - it
participates in the regulation of cell growth and division, the
transmission of signals to cells; increased tyrosine kinase
activity (e.g., the epidermal growth factor receptor EGFR) can
lead to tumor growth. For many kinases, the names originated in a
more complex way based on the diseases they were discovered to
study. The so-called ATM kinase ( Ataxia
Telangiectasia Mutated ) is particularly important for our
area of ??biological effects of radiation , which phosphorylates
and increases the expression of the p53 protein , which
acts as a transcription factor and is essential for cell cycle
regulation and induction of apoptosis. discussed below " Mechanisms
of Cell Death ", "Apoptosis
"). It is also the anti-apoptotic protein Bcl-2
( B cell lymphoma leukemia-2 ) and, conversely, the proaptotic Bax ( Bcl-2 associated X protein ) .
Cyclins are proteins that are
present in the cell mainly in a certain part of the cell cycle;
During the cell cycle, there are cyclic changes in their
concentration (hence their name) - expression and degradation, which plays an important
role in cell cycle regulation.Cyclins contain homologous chains
of about 100 amino acids in size.They bind to their partners - cyclin-dependent
kinases CDK. At low cyclin
concentrations, most CDKs are in an inactive free state. As the
concentration increases, cyclins may bind to certain CDK
regulatory sites, causing an increase in their activity - active
CDKs can phosphorylate a number of other enzymes, causing their
activation and deactivation, which can significantly affect cell
cycle dynamics. Due to the complicated regulatory mechanisms in
eukaryotic cells, several species of cyclins and their respective
CDKs are present, regulating different phases of the cell cycle: cyclins
D (regulating the passage of the control node in the late G1
phase), cyclins E (affecting G1 to S phase transition), cyclins
A (controlling the course of the S phase), cyclins B
(controlling the onset of mitosis and some processes of its
course).
The simpler substances of a proteinaceous
nature are the so-called peptides (Greek pepto = boil, digest ; they are formed,
among other things , by digesting proteins) . They also consist of amino acid chains, but in smaller
numbers, about a few dozen (peptides were mentioned at the
beginning of our discussion of cells). They are used for cell
communication, eg in the immune and nervous systems, and include
a number of hormones . This group of substances of
proteinaceous nature includes cytokines (Greek: kytos = cavity, cell, kineo = moving,
transmitting ) produced by cells and
used for their interaction and transmission of information. These
include, for example, interferon (lat.
Inter = between, fero = to carry ) andinterleukins
( the interaction of white blood cells
) .
DNA Modification and Damage
Some chemicals can penetrate the cell nucleus, interact with DNA,
and modify it in such a way that it cannot successfully transmit
genetic information during cell division. Such substances can
slow down or stop cell division - they are called cytostatics
. Such affected cells eventually undergo mitotic death
, mainly in the form of apoptosis . Ionizing
radiation (and the chemical radicals induced by it) have
a similar effect , which will be discussed in detail below. Both
of these mechanisms are used to kill tumor cells during
chemotherapy and radiotherapy (§3.6 "Radiotherapy ").
A number of chemicals entering cells from the outside
and inside during metabolism or ionizing radiation can react with
nucleotides and alter DNA sequences - causing genotoxicity
. RNA from viruses can also enter the DNA of
eukaryotic cells (by reverse transcriptase ). and change
its genetic information; called. oncoviruses may be the
trigger for mutations leading to oncogenic transformation of
cells.
The
cell wall
protects the cells, separating the cells from
the surrounding environment and from the other cells in the cell
separating processes in progress and provides control
cellular functions by acting as a selective barrier- membrane
. In eukaryotic cells, the cell wall is formed by a bilayer
phospholipid membrane. Cells receive chemical "signals"
from their surroundings (and possibly from other cells) and
respond to them. For simple bacteria, this is limited to the
perception of increased nutrient concentrations, but for
multicellular organisms, more complex and advanced forms of
communication with the environment function, including
intercellular communication. Intercellular communication involves
the whole chain: exclusion of a signaling molecule (eg hormone)
by the transmitting cell ® transport of the signaling molecule to the surface of
the target cell ® registration of the molecule by a receptor on the cell
surface ® transmission of the signal inside the target cell ®cell
response - induction of biochemical or biophysical changes in the
target cell. Small hydrophobic molecules similar to amino acids
(such as acetylcholine, dopamine, histamine, ...) can penetrate
the cell directly by diffusion through the phospholipid
bilayer of the plasma membrane - passive transport
. Transmembrane proteins , which form so-called ion
channels , are used to exchange some ions between the cell
and the environment .
Receptors
On the surface of cells (cell walls) there are so-called receptors
(Latin receptor = stimulus receiver
) - specific molecules that are able to
recognize other specific molecules in the environment, chemically
bind them and transport them inside the cell, or influence the
flow of ions through the plasma membrane through an ion channel.
A substance (molecule) that is able to selectively bind to a
cellular receptor is called a ligand (lat. Ligo = bind ) . The
ligand binds to the receptor and specific signaling inside the
cell is triggered. In terms of structure, the transmembrane
receptor consists of three basic parts (domains) :
- The extracellular domain , formed by the
amino-terminal end of the receptor protein, has a ligand binding
site;
- A transmembrane domain that anchors the molecule
in the cell membrane;
- The intracellular domain , formed by the
carboxy-terminal C-terminus of the macromolecule, triggers signal
transmission after its activation - it activates other molecules
of the signaling cascade in the cytoplasm, or to the core.
Receptor activation occurs by kinases
and phosphorylation , as mentioned above in the section
" Proteins, enzymes, kinases". Ligand binding
and receptor phosphorylation alter the conformation (spatial
arrangement, rotation - other isomerism) of this molecule and the
internal domain to reveal the binding site for specific
intracellular signaling molecules; kinases are used to activate
other molecules of the signaling cascade. signal is transmitted
to the nucleus are phosphorylated transcription factors activated
thereby induce transcription (or. repression) specific genes
producing and appropriate effector proteins (lat. Facio = do, efficio = power ).
Cytoskeleton
- skeleton and the holder of cell functions
Cytoskeleton - " cell skeleton"
(cellular "grid" or matrix) - is a system of mechanical
support and" reinforcement "of eukaryotic cells. It
consists of a complex mesh of fibrous protein structures in the
cytoplasm. These structures are of three types :
- Microfilaments (lat. filamentum = thread, fiber ) are the thinnest fibrous structures (thickness approx.
5-7 nm), which by their contractility move the cells as a whole,
using the energy obtained by ATP cleavage (see below)
Microfilaments are increasingly contained, for example, in
specialized muscle fiber cells
- Intermediate filaments
are formed by slightly thicker protein fibers (approx. 10-15nm)
and ensure the mechanical stability of cells and tissues against
mechanical stress
- Microtubules (lat. tubulus = tube, tube ) are the thickest and most complex structures of the
cycloskeleton (diameter about 20-30nm). They are thin hollow tubes
composed of a protein called tubulin , arranged in long
chains of dimeric units in which alpha- and beta-tubulin
molecules alternate . These fibers are helically twisted (13
dimers of alpha and beta tubulin form one complete thread) and
the individual threads are "laterally" bound to the
tube. Tubulin molecules contain binding sites for guanosine
triphosphate(GTP). Tubulin polymerization, associated with
microtubule elongation, occurs by sequential attachment to that
end of the microtubule ("+" end) that contains
beta-tubulin with bound GTP. Hydrolysis of GTP produces GDP ( guanosine
diphosphate ) and further fiber growth is stopped. The
opposite process to polymerization - dissociation ,
consisting in the separation of tubulin dimers from the end of
the fiber containing alpha-tubulin ("-" end), leads to
the gradual depolymerization and shortening of
microtubules. The assembly and degradation of microtubules is
controlled by proteins called MAP ( Microtubule Associated
Proteins ). Microtubules with their ends ("-") are
"anchored" in the central part of the cell in the
so-called centrosome, bodies in close proximity to the
nuclear membrane, which plays an important role in cell division.
Intracellular movement
and transpost
is one of the essential properties of cells, which is necessary
for carrying out basic biological processes. Intracellular
movement is mediated by the cytoskeleton, to which a number of
special proteins can bind. Along the microtubules, a number of
important molecules are transported in the cell. It is
through special substances called kinesins
that have binding sites for different molecules. Kinesins as
"molecular machines" move - "walk" - along
the hollow fibers of microtubules (by means of dinein
"molecular motor" bonds, which contact the microtubules
with rod protrusions) as along a "cableway" and thus
transfer temporarily bound molecules. To drive each step, an
adenosine triphosphate (ATP) molecule is used, which alternates
with the kinesin terminals, hydrolyzing the adenosine
triphosphate (ATP) to adenosine diphosphate (ADP) and cleaving
the phosphate. The released chemical energy is converted by
electrical polarization into a mechanical force
, causing movements and transport of molecules. In one such step,
the kinesin is shifted by a distance of two tubulin dimers, about
10 nm. In one second, a kinesin molecule can perform about
80 steps.
Cytoskeleton is not a fixed and rigid
structure, but a highly flexible and dynamic a
system that is constantly adjusted to the needs of the cell.
Unlike the usual concept of a skeleton
(human skeleton, skeleton of a structure). The changes in the
structure and size of cytoskeleton units are caused by
polymerization and depolymerization (decomposition, dissociation)
of proteins into chains and fibers (with a helical spatial
structure - in the case of microtubules). There is a constant
supply of cytoskeletal proteins (tubulin, actin) in the cell;
these monomers then polymerize into cytoskeletal structures or,
conversely, disintegrate back into monomers. The cytoskeleton
transforms chemical energy into mechanical energy - it is
responsible for all types of cellular movements, intracellular
(organelle movement, cell division) and extracellular (movement
of cells, flagella, cilia ...). Furthermore, the cytoskeleton
interconnects individual cell structures. And not just
mechanically. Along the cytoskeleton fibers, especially
microtubules, various proteins interact and transmit chemical
signals, necessary for the regulation of cellular processes. It
mediates the intracellular transfer of complex molecules between
the nucleus and other organelles, it also participates in cell
division (during cell division it creates mitotic spindle
).
In somatic cells, which are part of
tissues and organs, the cytoskeleton is connected outside the
cell by the so-called extracellular matrix : a
system of protein fibrin and collagen fibers (lat. Fibra = fiber , Greek kolla = glue
) , connecting the cells and holding them
together in tissues and authorities. It ensures the connection
between cells, maintains the integrity and shape of tissues,
transmits movement. The intercellular space itself is filled with
a fluid of gel consistency (interstitial fluid, "tissue
fluid"), which serves to transfer nutrients and oxygen to
the cells and to remove metabolic waste products.
Cellular organelles
Mitochondria - "power
plants" of the cell
Important organelles in the cell are mitochondria
(Greek mitos = fiber, chondros = grain - they have a
diverse shape from elongated fibers to compact grains, size about
0.1-2 m m).
They have two membranes, inner and outer :
- The inner membrane is irregular, many times bent (depressions into the interior are sometimes called kristy
) . It is selectively permeable only to
molecules involved in the respiratory chain and oxidative
phosphorylation. Multiprotein complexes are located on the inner
membrane, which mediate cellular respiration by proton and
electron transport; cytochrome c is particularly
important for our interpretation (see
"Apoptosis" below) .
- Outer membraneit resembles a cell wall and is
permeable to most small molecules, but not to more complex
protein molecules (such as cytochrome c). It developed during the
phylogenetic development of the plasma membrane of aerobic
bacteria after their endocytosis (see
below) .
The main function of mitochondria is the
production of chemical energy in the form of molecules
ATP (adenosine triphosphate) C 10 H 8 N 4 O 2 NH 2 (OH) 2 (PO 3 H) 3H. ATP molecules, which are "energy
transporters" in cells, are formed in mitochondria by
oxidation of citrates and fatty acids (Krebs cycle, hydrogen
oxidation, oxidative phosphorylation). Where necessary, ATP is
oxidized to ADP (adenosine diphosphate + P) or AMP (adenosine
monophosphate + 2P) to release considerable energy (approximately
57 J / g). Mitochondria are sometimes referred to as "power
plants" of cells in which the oxidation of nutrients,
especially glucose, to carbon dioxide, water and output ATP,
whose energy is used in cells for endothermic processes -
macromolecule synthesis, transport of molecules against the
gradient, cell movement ( including muscle contraction),
formation of electrical potentials in membranes, heat production.
Mitochondria are formed in cells by continuous binary
division ("budding", similar to bacteria)
independent of the cell cycle; inside the inner membrane they
contain their own mitochondrial DNA , completely
different from nuclear DNA.
Mitochondria have an interesting
evolutionary origin: they probably evolved about 1.5-2 billion
years ago from aerobic bacterial ancestors in the
endosymbiosis of primary eukaryotic cells with a certain type of
bacteria (similar to protobacteria of the order Rickettsiales)
that phagocytosed *). The cell obtained oxygen and nutrients from
the environment, passing them on to bacteria - future
mitochondria - which metabolized them into energy molecules for
their own needs as well as the needs of the whole cell. Such a
symbiosis has proven to be mutually beneficial. Over the millions
of years, the cell has completely "tamed" its bacteria,
the endosymbiot has given up most of its independence and become
a mere organelle. Circular DNA, similar to prokaryotic
nucleotides, is still present in mitochondria and ensures their
partial genetic autonomy. In plant eukaryotic cells, chloroplasts
(a kind of photochemical "battery") occur instead of
mitochondria , whose similar evolutionary origin is derived from
endosymbiosis with cyanobacteria .
*) Trace phylogenetic
"evolutionary tree" eukaryotes to
the" root " is very difficult. In addition to the primary
endosymbiosis somewhere in the beginning, there were during
the evolution of several other secondary or tertiary
endosymbiózám . Comparative analysis of morphological
characters are often misleading. A more reliable method is now molecular
phylogenetics , which has developed procedures for
By comparing gene sequences (most often genes for small ribosome
RNA, SSU rRNA, which are present in all cells) in different
organisms, certain similarities can be traced, which may be
indications for their phylogenetic relatedness. that gene
fusions very often occurred during evolutionoriginally
separate genes and vice versa to gene divisions into two
new parts. Therefore, it is necessary to perform phylogenetic
studies on multiple genes and proteins - multigene or phylogenomic
analyzes using sequencing of genomes and mediator mRNA
molecules, followed by statistical analysis of similarities.
Lysosomes
Other organelles in the cell are lysosomes
("digestive bodies"), in which chemical decomposition -
hydrolysis - of various more complex organic substances
(sugars, fats, nucleic acids, proteins) takes place in an acidic
environment with many different enzymes. The products of this
decomposition can then be processed in mitochondria to
form ATP energy molecules that "distribute" the binding
chemical energy needed to synthesize complex substances and other
cell functions.
Ribosomes - "factories" for proteins
Ribosomes (ribonucleon protein
particles) are small organelles found in large numbers in the
cytoplasm of cells and also on the surface of the endoplastic
reticulum. They are composed of RNA and proteins, structured into
two subunits. The small subunit of the ribosome has a molecular
weight of about 800 kDa and consists of 20 proteins and an RNA
molecule of about 1600 nucleotides in length (16S RNA). The large
ribosome subunit is about 1500 kiloDaltons in size and consists
of 33 proteins and two RNA molecules (23S RNA of 2900 nucleotides
in length and 5S RNA of 120 nucleotides in length). In
ribosomes, proteins are synthesized from the mRNA strand by translation - decoding information from the
mRNA according to which the resulting amino acid sequence is
assembled; tRNA molecules are used for "reading" which
carry an amino acid on the one hand and a triple nucleotide
(anticodon) on the other hand which can be paired with an mRNA
codon (as described above). Specific nucleotides of 16S RNA from
the small subunit of the ribosome form hydrogen bonds with codon
and anticodon nucleotides only when properly paired and
geometrically oriented. The actual peptide covalent bond, which
connects two amino acids, is formed in a large subunit of the
ribosome, where the so-called peptidyl-transferase center
containing 23S RNA and ribosomal proteins is located. Ribosomes
are a kind of cellular "line" or "factory"
for protein production: nuclear DNA (" design
office").') Supplies information mRNA ( " technical
drawing "), which is reacted on ribosomes translates
into the amino acid sequence of proteins (via transfer tRNA
for each amino acid) - extends own "production" of a
molecule specific proteins.
Other organelles
Relatively large formation in the cell's endoplasmic
reticulum ( in the microscope it
appears as a kind of "clot" in the cytoplasm) in the shape of a coiled membrane sheet, consisting of two
types: a rough (granular) reticulum whose surface is
dotted with ribosomes (these granules cause
"roughness") and a smooth endoplasmic
reticulum with a network of channels connected to the rough
reticulum. These units play a central role in the synthesis of
proteins, lipids, steroids and other substances in the cell. Golgi
complex is endomembrane system vesicles ( vesicles
) in the vicinity of the endoplasmic reticulum, for transporting
and modify proteins.
Cell
specialization
Multicellular organisms consist of cells of different species
that have different shapes and different activities - they are
" specialized " to create different
differentiated tissues and organs with a specific function, or to
mechanically build, for example, a supporting or locomotor
system. These specialized cells, performing a certain function,
are called effectors (Latin
effector = executor ) . There are
about 230 species of various specialized cells
in the human body . These are, on the one hand, body cells - somatic
(Greek solo = body ) - these are practically all cells in the body, and
sexual cells - gametic (Greek
gamete = woman, wife)) - in
mammals they are eggs and sperm.
To ensure growth and
regeneration, stem cells (maternal, clonogenic)
are also present in the tissues and organs . Stem cells are
capable of unrestricted division, being able to produce both
identical stem and daughter cells, bearing the characteristics of
a given differentiated tissue - asymmetric division
into two different cells, an identical stem and a different
daughter cell *). Asymmetric division ensures the process of differentiation,
in which the emerging cells by their structure and function adapt
to the specific role they are to play in the organism. All cells
in the organism are provided with the same genetic equipment, but
as a result of this process, only a certain part of genetic
information is realized in a particular cell (due to specific transcription
factors , only certain genes are transcribed in the
cell, others are not applied). Daughter effector cells usually
enter the quiescent G0 phase of the cell cycle.
*) Cell division and cell
cycle are discussed below in the section " Effects of radiation on cells ", section " Radiation effects
during the cell cycle ".
New research has shown that specialized
effector cells can, under certain circumstances (eg due to stress
from an unfavorable environment, such as a change in the acidity
of the environment), lose their specialization
and become cells that have all the genetic equipment available.
The division of these cells may appear to be involved in the
regeneration of damaged tissues; it is also speculated that some
cells, after losing specialization due to mutations, may
transform into clonogenic tumor cells.
Extinction
- death - of cells
Extinction of
living organisms
No organisms live forever - they are " deadly
". The causes of extinction (death) of
organisms can be very diverse, but we can roughly divide them
into two categories:
1.
External causes
- mechanical destruction, attack and "eating" by
another organism, thermal damage, chemical or radiation damage,
adverse change in external conditions, lack of nutrients.
2. Internal
factors - physiological disorders and diseases,
"wear and tear" of organs and degeneration of vital
functions, aging - senescence .
External and internal factors are often closely related.
Infections, radiation or chemical pollutants, even if the
organism successfully copes with them in the acute phase, can
initiate latent processes of internal degradation, which can
eventually cause the extinction of the organism ...
Aging of organisms
Aging - senescence - of a living
organism is a complex irreversible process by gradually reducing
the efficiency of vital functions and decaying the body's
structures. It is an integral part of the life of all
multicellular organisms and will eventually result in their
extinction. The rate of senescence is a fundamental limiting
factor for the life span of organisms. This
maximum life span is very different for each
species of organism.
The longest living
organisms are some conifers - Sequoia sempervirans or Pinus
aristata , reaching 3000-5000 years. Examples of animals are
long-lived turtles such as Chelonoidis nigra
(approximately 200 years) or bivalves Arctica islandica
(500 years). Most animals have a life span of years or decades,
in insects they are usually months, the shortest is in mayflies
(max. 3 days).
Aging is a multifactorial
process involving various mechanisms, of which three are probably
the most important :
- >
Reactive free radicals, especially oxygen, formed during
many metabolic processes in the body. The main source of free
radicals in cells are mitochondria , in which
cellular respiration and the production of chemical energy take
place. Although antioxidant enzymes are present in
organisms , the ability to produce them decreases with age. Free
radicals then begin to accumulate more and can damage cells and
tissues (especially causing DNA strand
breaks, as described in the following section) .
- >
Accumulation of DNA defects arising spontaneously and
accidentally during life due to replication errors, oxygen
radical reactions, or mutagenic reactions (which
usually enter cells from the environment with food). Some of these more serious defects in important
genetically coding parts of DNA are not repaired, they accumulate
in the organism, and the proper functioning of cells in tissues
can occur. It is observed that the number of spontaneous
chromosomal aberrations in somatic cells increases with age.
- >
Shortening of telomeres in mitotic cell division (described above in the section " DNA, RNA, proteins, chromosomes, telomeres ", passage " Telomeres "). After exceeding a certain critical length, the
telomeres lose their protective function and the cell can no
longer divide; usually programmed cell death - apoptosis -
occurs. The regular shortening of telomeres during each division
means that somatic cells can perform only a limited number of
divisions during their lifetime - about 50-80 .
This number of divisions is called the Hayflick limit
(Hayflick and Moorhead found out in 1951) . Therefore, the cells capable of dividing are becoming
less and less in the organism over time, the functional capacity
of the tissues decreases and therefore the organism ages - replicative
aging .
Note: The
aging process - senescence - is sometimes related to the
2nd law of thermodynamics - growth entropy
(disorder) of closed systems. However, this 2nd law of
thermodynamics is only a hidden physical
framework lying deep in the molecular background. However, the
real explicit mechanisms here are the biochemical processes of
free radicals, DNA defects and telomere shortening during cell
division.
Mechanisms of cell
death
At the cellular level , we encounter four basic
types - mechanisms - extinction and inactivation: apoptosis,
autophagy, necrosis and senescence of cells. "Mitotic
catastrophe" is sometimes mentioned as a special category.
Under physiological circumstances, eukaryotic cell death is one
of the mechanisms for maintaining tissue homeostasis
balance in the production of new cells and the extinction of old,
redundant, damaged cells. It can also serve as protection against
mutated cells, which can be dangerous for the body.
Cell
apoptosis
The basic method of controlled (programmed) death of damaged,
dysfunctional or otherwise redundant cells in multicellular
organisms is called apoptosis (Greek apoptosis = falling - the name comes
from the fall of leaves caused by the death of cells in the
petioles) - a kind of cellular
"suicide". It is a complex chain of processes
influenced by a number of factors and controlled by many complex
biochemical molecules, especially proteins and enzymes. Apoptosis
can be induced by two types of stimuli :
¨ Intracellular activation of
apoptosis - irreparable DNA damage, toxic
substances in the cell (eg oxidation products), lack of
nutrients. Apoptosis triggered by internal mechanisms acts
as a protection against the survival and proliferation of
defective cells, especially mutated cells with damaged DNA .
¨ External (extracellular) activation of
apoptosis - binding of certain substances (ligands
of "death"), transmitted by regulatory mechanisms of
tissues and the organism, on the relevant receptors of the
cytoplasmic membrane. Properly functioning apoptosis,
triggered by external regulatory mechanisms from the tissue,
helps maintain tissue homeostasis and provides effective
protection against excessive cell proliferation.
Above: Internal and external signaling pathways
of apoptosis activation. Bottom: Morphological
changes of the cell during apoptosis.
Internal signaling pathway
of apoptosis
The p53 protein (having a
molecular weight of 53 kilodaltons and a length of 393 amino
acids) plays an important role in
apoptosis, especially in the process of internal activation of
apoptosis . Under normal circumstances, its level in the cell is
low (maintained by the mdm2 protein ), which is
sufficient to maintain cell cycle regulation. DNA damage
activates ATM kinase , which triggers
the production of DNA repair proteins and (via mdm2) activates
and phosphorylates the p53 protein , which acts as a
transcription factor. In the early stages, p53 can activate DNA
repair (via GADD45 proteins ) and slow down the cell
cycle (via p21 proteinencoded by the WAF / CIP1 gene) so
that repair is sufficient. The p21 protein inhibits cyclin-dependent
CDK kinases and arrests the cell cycle in the G1 phase; in
the case of proper function of p53, the cell cycle is restored
only after the elimination of errors in DNA. If p53 detects DNA
damage beyond repair, its expression is increased, thereby
inducing the synthesis of Bax and other
mitochondrial-binding proteins; at the same time, the
anti-apoptotic Bcl2 protein (mentioned below) is
inhibited . Mitochondrial membranes lose potential and become
permeable; cytochrome c *) is released from mitochondria
), DIABLO protein (direct IAP
binding protein with low pI) , AIP
( Apoptosis-Inducing Protein) and the caspase chain is started (see below).
*) Cytochrome c , if it
is inside the mitochondria - located on the inner membrane
(through which it mediates electron transport), is important for
cellular respiration (there is cytochrome-c-reductase and
cytochrome-c-oxidase). However, if released from the
mitochondria, it can lead to cell death.
Thus, the p53 protein
(discovered in 1979 in the British Cancer Research) has the
function of a cell cycle regulator and a kind of "guardian
of the genome" :
- It can activate DNA repair, while pausing the cell cycle to
allow time for repair mechanisms;
- If it turns out that the cell's DNA is so severely damaged that
its repair is no longer possible, it can trigger apoptosis, which
programmatically leads the cell to "safe" extinction.
In this way, the organism is protected
from potentially dangerous cells with a damaged genome, ie also
against tumor cells. Hence the name tumor-suppressor gene TP53
for the corresponding DNA sequence (located at 17p13.1), which
encodes as a product (transcription factor) the p53 protein.
Mutations in the TP53 gene can lead to tumor growth (along with other factors, see §3.6 " Radiotherapy
", section " Carcenogenesis
") . Several other genes (cooperating
and competing) are also involved in the function of TP53.
External signaling
pathway of apoptosis
External activation of apoptosis is initiated by the arrival of a
"deadly" ligand that binds to the
appropriate "deadly" receptor located
on the cell surface. One such ligand is the so-called TRAIL gene (the name comes from the field of oncology: tumor
necrosis factor-related apoptosis-inducing ligand ) . Below the cell surface, pro-caspases are then
activated (8 and 2), the process branches to the inhibition of
the mitochondrial membrane (and the release of cytochrome c
as in the above-mentioned internal activation) and to the direct
activation of effector caspases (-3,6,7).
Caspase chain
The actual phase of irreversible apoptosis is caused by the
activation of proteins from a group of cysteine ??proteases
called caspases *) (abbreviation caspase =
cysteinyl aspartate-specific protease ), which
break down intracellular proteins (proteolytic degradation),
including the cytoskeleton and cell matrix; this then leads to
the morphological changes of the cell mentioned below. They also
attack the nucleus and cleave DNA.
*) So far, 14 species of
caspases are known, of which about half are involved in
apoptosis. Some of them, so-called pro-caspases
(-2,8,9,10) in inactive form, commonly occur in the cytoplasm. By
reacting these "signaling" caspases with cytochrome c,
or association with receptors, effector caspases
(-3,6,7) are expressed, which break down proteins and other
macromolecules in the cell.
After starting the apoptotic
process the DNA cleaves into smaller sections,
hydrolysis of cellular proteins, degradation of cycloskeletal
structures and organelle membranes takes place. Furthermore,
there is a membrane depolarization of the cell
wall, the detection of phospholipids on the cell
surface, increased permeability of the plasma
membrane, and later the violation of the integrity of the
cell wall. In the final phase, the cell
shrinks and breaks down into several smaller fragments
(apoptotic bodies), on the surface of which molecules (eg phosphatidylserine - PS) stimulate
their phagocytosis -
"ingestion" by surrounding cells, phagocytes or immune
cells ( macrophages).- increased
exposure of PS on the cell surface is an attractive signal for
macrophages: " eat me! ") . Thus, unlike necrosis, there is also a regulated and
gentle "clearance" of cell death products.
Apoptosis is the main mechanism of
biological action - cell death - when irradiated with low
and medium doses, tenths to units of Gy. In the
induction of apoptosis by ionizing radiation (internal signaling
pathway), the mechanism of its occurrence and time dependence
differ significantly in different cell types. Rapidly dividing
radiosensitive cells can enter apoptosis from different points in
the cell cycle, less radiosensitive cells show varying lengths of
"blockage" at some stage of the cell cycle, mostly in
the G2 phase. At this time, the cells do not divide and are given
time to repair the damage. If the damage is irreversible,
apoptosis is initiated. The total time that cells have available
to repair DNA damage before eventual entry into apoptosis is an
important factor in the radiosensitivity of these cells at lower
doses (2-5Gy). At higher doses (approximately 20 Gy), ionizing
radiation-induced apoptosis occurs independently of cell blockage
at a certain stage of the cycle and time,
An interesting effect accompanying the
apoptosis of specific irreversibly damaged cells is the so-called
bystander effect (discussed below), leading to apoptosis
or genetic changes in some surrounding cells that were
not originally damaged.
Inhibition of
apoptosis
Antiapoptotic mechanisms may also be involved in cells
and tissues . Some mutations in the TP53 gene (deletion or point
mutation) can cause inhibition of apoptosis. Apoptosis can also
be blocked at the mitochondrial level. The antiapoptotic gene Bcl-2
( B cell lymphoma / leukemia protein 2 - was isolated
from tumor cells of lymphoma B), which is found in mitochondria
and whose increased concentration protects mitochondrial
membranes - prevents the penetration of cytochrome c and
the triggering of the caspase chain of proteolytic degradation in
the cytoplasm (blocks the effect of p53 protein). Bcl-2 is
intensively expressed by its BCL-2 gene during
embryonic development; in adulthood it occurs only in stem cells
(and in tumor cells).
Both Bcl-2 and BAX are transcriptional targets for an
important regulatory protein p53. Expression of the pro-apoptotic
Bax protein can be induced by ionizing radiation,
cytotoxic agents (such as chemotherapeutics), or other genotoxic
stress.
Cell
autophagy
This is a kind of "self-ingestion" of a cell (from the Greek auto = himself, fago = eat, devour
) . During complete autophagy
(macroautophagy) of cells, autophagocytosis , the
walls of lysosomes are disrupted and the cell content is
subsequently degraded (decomposed, "digested").
Autophagic vacuoles form in the cell, after which the process of
autophagy can affect the whole cell. Autophagy can be induced by
cytotoxic substances or radiation, under physiological conditions
it acts as an adaptation mechanism to a lack of nutrients or
oxygen. Partial autophagy- a controlled process of
self-cleavage and digestion - occurs when a cell tries to survive
adverse conditions by digesting part of the cell cytoplasm or its
less important organelles. Autophagic vesicles are transported to
lysosomes, in whose acidic environment complex biological
molecules decompose, recycling energy and necessary substances.
This maintains protein homeostasis during adverse conditions;
after their disappearance, the cell can continue to function and
divide.
Cell
necrosis
The direct death (extinction) of
cells, which is practically not controlled by cellular
mechanisms, is called necrosis (Greek necrosis = dead ). It arises as a
result of severe irreversible damage to cells - mechanical
damage, chemical damage, strong overheating or hypothermia,
hypoxia, strong radiation. Oxidative phosphorylation is stopped,
ions accumulate in the cell, cell edema (enlargement) occurs,
organelle membranes rupture and proteolytic enzymes are released
into the cytoplasm. Protein and DNA are broken down, the cell
wall is broken, and the degraded cell contents spill into the
extracellular space, which is accompanied by an inflammatory
reaction in the tissue. Necrosis can affect entire groups of
adjacent cells ( tissue necrosis ).
When irradiated with ionizing radiation, cells are
necrosis at very high doses of tens to hundreds
of Gy.
Cell
senescence
Cell aging ,
called senescence , is a long-term multifactorial
process involving both intracellular "program"
molecular mechanisms and time-accumulating exogenous detrimental
factors affecting cell viability. Progressive damage to cells by
reactive oxygen and nitrogen during the life of tissues is
applied, with the ever-decreasing capacity of antioxidant
mechanisms. Cells can only reach a certain limit in the number of
their divisions, the so-called Hayflick limit (about
40-60 cycles); then the cells lose their ability to divide. The
limited replication potential of cells is mainly due to the
shortening of the so-called telomere- they are
marginal complexes in DNA that protect the ends of chromosomes
from adverse reactions and binding and from their evaluation by
cellular mechanisms such as DNA breaks. During DNA replication,
there is no complete synthesis of the DNA ends, so at each cell
division, the marginal ends - telomeres - are shortened to the
daughter DNA. With excessive truncation, telomeres no longer
adequately protect the ends of chromosomes, which evaluate cell
control mechanisms and stop the cell cycle. Telomere shortening
thus functions as a "mitotic counter". After reaching
the Hayflick limit, cells age , replication senescence
occurs (cf. also the passage " Extinction - death - cells " above) .
However, there is a special enzyme called telomerase
(it is a complex composed of RNA and
proteins, containing sequences serving as a template for the
synthesis of DNA telomere sequences - reverse transcriptase
) , which is able to synthesize the
terminal sequences of telomeres and thus prevent their shortening
during cell division. Such cells are then capable of unrestricted
division ( immortilization -
"immortality" of cells), which physiologically takes
place only in dividing embryonic and stem
cells, while pathologically it is applied in tumor cells
(§3.6 " Radiotherapy ").
Senescence can be accelerated by some
harmful chemical factors, as well as exposure to ionizing
radiation (aging of skin cells accelerates excessive sun
exposure) - premature stress-induced senescence (a
regulatory pathway of senescence independent of telomere
shortening leads through the p16 protein ).
Entoze
cells
Entoze cells (from the Greek. Entos
= inside
) is a phenomenon where two cells connected
to each other and combined in one cell,
temporarily or permanently - one cell is "internalized"
inside another, a "cell within a cell" is formed. In
laboratory cell colonies, it is occasionally observed under a
microscope that two cells gradually approach each other until
they "enter" each other, "invading" one
living cell into the cytoplasm of another cell. In many cases, it
is "cannibalism", where one cell absorbs another, which
disappears due to lysosomal enzymes - this could be classified as
cell death (as is the case with phagocytes).
However, sometimes endosymbiosis occurs , when
the absorbed cell survives, it may even divide inside the
"host" cell, or it may leave it again without damage.
Entosis occurs in cells that have separated from
binding in the extracellular matrix. As such a released cell
approaches close to another cell, adhesion forces to the
cytoskeleton of a neighboring cell begin to act on it, which can
push it inward. So far, the question is whether entosis is a
phenomenon that actually occurs in the body (where cells are
fixed in the tissues in the extracellular matrix) or only in free
cell cultures ..? .. Entosis could play a role in cancer. It is
not yet clear whether positive (another type of cell death that
can help reduce tumor cells) or negative (tumor cells can
"hide" in other cells from immune mechanisms or
chemotherapeutics and then relax again and begin to multiply)..?
..
Mitotic
catastrophe
This is sometimes referred to as a more complex combined
mechanism that may (but may not) result in cell death. It occurs
as a consequence of erroneous mitosis when a
cell attempts to divide without proper repair of damaged DNA (as
in Figure 5.2.2c), due to failure in the G2 / M control node and
premature activation of CDK1. In a mitotic catastrophe, a larger
number of multipolar dividing spindles and decondensed
chromosomes appear, nuclear fragmentation or loss of the nuclear
membrane occurs, two or more nuclei may be present ( multinucleation)
caused by an inaccurate distribution in ecoconesion. This
situation can lead to "secondary" mitotic cell death,
mainly by the mechanism of apoptosis or autophagy. However, if
the process of apoptosis is inhibited, asymmetric multipolar
division may occur, resulting in aneuploid cells with gene
mutations or chromosomal instability.
Note: Faulty
mitosis can also occur due to the action of certain chemicals
that attach to the microtubules and prevent them
from polymerizing or depolymerizing. Depolymerization of
cytoplasmic microtubules and polymerization of new microtubules
(astral, polar, kinetochore) around centrosomes at the nuclear
membrane, forming a dividing spindle, is one of the key
articles in cell mitosis. The respective anti-tubulin substances
(microtubule inhibitors) are therefore referred to as mitotic
poisons . Of the natural plant substances, it is, for
example, colchicine (an alkaloid contained in ocun),
which causes inhibition of microtubule polymerization, or taxol
(the alkaloid paclitaxel contained in yew), which causes
inhibition of depolymerization. However, the targeted
intervention of microtubular inhibitors in cell division can be
used to stop the growth of tumor cells (§3.6 " Radiotherapy
", passage "Chemotherapy").
Immune
cell death
In multicellular prokaryotic organisms, complex interactions of
various specialized cells occur. During evolution, the immune
system evolved, whose task is to protect the body from foreign
cells - especially infection by external intruders, but
also from its own damaged or mutated cells. ----....... The main
biochemical molecules mediating immune protection are proteins
from the group of immunoglobulins . ..
...........
Although immunoglobulins can also induce apoptosis, the main
mechanism of immune killing of unwanted or
"suspicious" cells is the activation of
complements - membrane glycoproteins C1-C9, which by
their proteolytic effects attack cytoplasmic cell membranes and
they cause their penetration . The cell
diesand released chemicals cause an inflammatory
reaction with leukocyte accumulation. Unlike apoptosis, this is
the external proteolytic destruction of the
cell. Another mechanism of immune cytocides is the induction
of phagocytosis - the fixed Fc region of bound antibody
specifically binds to the Fc receptor of some types of
leukocytes, especially macrophages, which then recognize and
subsequently phagocytose tumor cells. ............
These cell killing mechanisms are used in biologically
targeted cancer therapy using monoclonal
antibodies (§3.6 " Radiotherapy
", passage " Monoclonal antibodies ") .
...........
Further details of the structure of cells and their
chemical and biological functions lie beyond the scope of this
physically focused treatise.
Mechanisms
of the effect of radiation on living matter
Free radicals
One of the basic chemical phenomena in the irradiation of
substances, especially substances containing water and more
complex compounds, is the formation of free radicals
. Free radicals are those atoms and molecules that have one or
more unpaired electrons in the last orbit of the electron shell.
Such an atom or molecule is then highly unstable and reactive
*). It tries to reach an equilibrium state by obtaining another
electron "into a pair" from the surrounding molecules.
In this reaction, a molecule that has lost an electron can become
a new radical. Free reactive radicals, due to their oxidative and
reducing effects, are able to cleave various
types of internal molecular bonds in biomolecules and degrade
thus their chemical structure, necessary for the respective
biological functions.
*) In addition to free radicals,
some other substances whose molecules do not have unpaired
electrons show similar properties of high reactivity. It is, for
example, hydrogen peroxide H 2 O 2 , hypochlorous acid or atomic oxygen
O 1 .
These substances are also formed during irradiation and
contribute to biological effects (especially in the increased
presence of oxygen - see " oxygen effect "
below).
Free radicals enter into many reactions in
the biological environment. It is, for example, lipoperoxidation
of fats (with the formation of aldehydes), oxidation of
proteins , glycation proteins with glucose, changes
in RNA and DNA strands that can lead to cell death or kk
mutations (see below).
Over millions of years of
evolution, organisms have partially "learned" to use
free radicals to their advantage. Examples are white blood cells
containing precursors and enzymes that are capable of generating
free radicals; they then participate in the elimination of
bacteria in the phagocytes. In terms of the biological effects of
radiation, however, we will deal mainly with such reactions of
free radicals that lead to cell damage .
Certain "opponents"
of free radicals are antioxidants. These
substances either prevent the formation of free radicals or the
free radical preferentially oxidizes this substance, which
counteracts the oxidation inside the cell. The best known
antioxidants are ascorbic acid (vitamin C), uric
acid (prevents the formation of hydroxyl radicals in the
blood plasma), cysteine, folic acid ; elements such as selenium,
magnesium, zinc, chromium , ...
Dominant
effect of radiation on DNA, genotoxicity
As mentioned above, ionizing radiation causes chemical and
biochemical changes in living tissue, which can generally damage
all parts of cells, cytoplasm, individual organelles. However,
the response of cells to radiation is determined primarily by the
behavior of DNA. Nuclear deoxyribonucleic acid
(DNA) is the most biochemically important macromolecule in a cell
- it contains basic information about the structure and function
of a cell. Interference with the biochemical structure of DNA can
cause a cell to stop producing the necessary protein, or it can
produce altered "foreign" proteins that do not fulfill
their function (sometimes they can be toxic).
DNA macromolecules are the dominant
"targets" for the biological effects of
ionizing radiation - there may be mainly breaks in the
sugar-phosphate chain and base changes. E.g. oxidation on an
amino group such as adenine produces an OH group to which
cytosine binds instead of thymine - an error
occurs in the amino acid chaining. On the DNA
double helix, the radiation can cause a number of damages (see
Fig. 5.2.2b), the main ones being two types of interruptions or
"breaks" :
× Single strand break ( SSB
),
damaging only one strand (strand) of DNA. These breaks are
usually easily repaired by the cell using the enzyme DNA
ligase .
× Double strand break ( DSB
)
affecting both strands (strands) of DNA. Here, repair is much
more difficult and often unsuccessful. A double break in the
structure of DNA often leads to the death of a cell - to its lethal
damage, it usually disappears by apoptosis (it
was described in detail above in the section " Mechanisms
of cell death ") .
Mechanisms for repairing DNA damage will be discussed below -
section " Repair processes".
The DNA fragments
micronuclei
When formation of double stranded DNA breaks often fails these
faults repaired. It can then be separated large DNA
fragment from the original double-stranded DNA, which
remains in the cytoplasm during cell division may enter the
cytoplasm of one of the daughter cells. Micronuclei
are fragments of chromosomes, encased in a nuclear membrane, tend
to be about 1/10 the size of a cell nucleus, and are well
observable under a microscope after chromatin staining.
During radiation exposure, other
biochemical molecules in the cytoplasm, cytoskeleton or
organelles - lipids, carbohydrates, proteins and others - are
also damaged in the cells. However, a large number of these
molecules are contained in the cells (and they are continuously
supplemented by the synthesis of other molecules) and a more
pronounced effect of radiation would occur only when a larger
percentage of these molecules were damaged; this occurs only at
relatively high doses of tens and hundreds of Gy. However,
significant DNA damage occurs even at lower doses (tenths to
units of Gy), when the effect on other biochemical molecules is
still small. Therefore, in explaining the mechanisms of the
effects of ionizing radiation on cells, we focus primarily on the
effects on DNA.
Note: Some
new radiobiological studies using very thin
"micro-bundles" of charged particles (mainly andand protons, but has also been shown on X-rays) have shown that direct DNA damage is not necessary to
trigger intracellular damage mechanisms. Even in the case of
cytoplasm irradiation , a kind of "remotely
induced" response ( bystander
response ) can occur , leading to
radiation damage to cells - apoptosis or genetic
changes (cf. the " Bystander
effect " discussed below ) .
Since DNA damage leads to disruption
or change of genetic information in the cell, we talk
about the genotoxic effects *) of ionizing
radiation and the chemicals induced by it in cells. Overall,
ionizing radiation acts as a cytostatic(cell
damage, cell division arrest) and mutagen
(damage or alteration of genetic information). For the harmful
effects of ionizing radiation on the organism, individual tissues
and organs, the collective name radiotoxicity is
used .
*) Genotoxicity is also
shown by a number of chemicals that enter cells
from the outside (through the body's metabolic pathway) or are
formed inside the cells (during internal metabolism of cells or
during ionizing radiation). These substances enter the nucleus,
react with DNA and cause deterministic (mitotic cell
death - cytostatics, stronger irradiation) or stochastic
effects.(mutations, tumor formation - long-term effects of
carcinogens or weaker radiation); see " Dose-biological
effect relationship " below. Also some viruses
( retroviruses, oncoviruses ) have a high genotoxicity:
the RNA of these viruses is able, by the action of reverse
transcriptase , to enter the DNA of eukaryotic cells and
change their gene sequence.
No specific genetic changes or mutations are known
that can be attributed to the effects of ionizing radiation and
distinguish them from changes caused by chemical action (external
or internal). The genetic effects of radiation are manifested
only by an increased frequency of spontaneously
occurring mutations and genetic changes.
Basic
stages of the effect of ionizing radiation on the organism
First, we clearly analyze the radiation effects from the global
point of view of the whole organism (in the
following explanation we return to the procedure: intracellular
mechanisms ® cells ® tissues ® organs ® organism) . The process of the
effect of ionizing radiation on living tissue takes place in four
significant stages, differing in their speed and the type of
ongoing processes (the relevant processes are schematically shown
in Fig. 5.2.1) :
Fig.5.2.1. Schematic representation of significant processes and
their time sequence in the effects of ionizing radiation on
living tissue.
Note: The scale on the time axis
is basically logarithmic, but in some sections it is slightly
modified so that it is possible to clearly draw individual
events.
Only the physical and chemical stage depends on
the physical parameters of the radiation , while
the subsequent radiobiological response of the cells is
determined only by the biological properties of the
specific cell types. It can be seen from Fig. 5.1, among other
things, that in most cases the interaction of quantum ionizing
radiation with living tissue has no effect . It
is when :
J occurs recombination of free radicals
before they just react with biologically important substances;
J Cell-level repair mechanisms
successfully repair DNA or other substance
damage;
J Cells killed by radiation are quickly replaced
by the division of healthy cells -compensatory
cell proliferation ;
J The body's
immune mechanisms recognize and destroy
genetically mutated cells.
The radiation effects
on the organism occurs mainly under two circumstances :
N When the body is irradiated with a high dose of
radiation, and terminates too many cells that
the organism is unable to timely replace;
N When the repair
mechanisms at the cell level do not successfully
and correctly repair all the damage and the
body's immune system does not recognize and
eliminate the mutated cells in time, which divide further.
All of these situations, which may
or may not result in biological effects, will be discussed in
more detail below.
Only a small
part of the absorbed energy of radiation is converted into
dissociation and binding energies of chemical reactions, the vast
majority of energy is ultimately converted into heat
. However, at doses used in biological applications, this radiation
heating is negligible .
Intervention and radical theory of radiation
effect
The effort to explain the effects of ionizing radiation on living
tissue led to the expression of two basic theories (or rather
ideas) - older intervention and newer radical
theory :
Fig.5.2.2. Radiobiological effects at the subcellular
level. a) Interventional and radical mechanism
of the effect of radiation on living tissue.
a) Above: When radiation enters
the DNA macromolecule, ionization and a direct destructive effect
occur. Bottom: Ionizing radiation interacts with
the water molecule, radiolysising of water occurs: H 2
O ® H +
+ OH - - formation of free
radicals . Highly reactive H + and OH - radicals attack
complex organic molecules and chemically change them
. DNA is disrupted in the nuclei of cells.
b) Different types of DNA damage due to
radiation and chemical influences (rough schematic
representation) . c) Radiation effects
during the cell cycle.
Share of intervention and radical
effect. Oxygen factor.
In organisms, complex biochemical molecules are dispersed mainly
in water. In the aqueous medium
(solution, suspension), the proportion of direct and indirect
effect depends on the concentration molecules of
biologically important substances. When irradiating dried
samples, the direct effect is mainly applied; in the case of
aqueous solutions, the share of the indirect effect is usually
dominant and the higher the lower the concentration. Inside the
cells there is an aqueous environment with a relatively high
concentration of biologically important molecules - the indirect
mechanism is dominant here, but it is necessary to take into
account the direct effect. The proportion of direct and indirect
effect also depends on whether it is sparsely or densely ionizing
radiation. The radical mechanism of the indirect effect
predominates in sparsely ionizing radiation. Densely ionizing
radiation produces such a high concentration of radicals that
they often recombine before these radicals can react with
biologically important molecules - an increased weight can
therefore have a direct effect.
The effect of ionizing
radiation also depends on the presence of oxygen - the so-called oxygen
effect . In the presence of oxygen, the radiolysis of
water produces strongly oxidizing peroxide radicals ,
which react irreversibly with the atoms in the DNA. Thus, the
presence of oxygen increases the radiation effects
, especially in sparsely ionizing radiation. In densely ionizing
radiation, where there is an increased proportion of the direct
intervention mechanism (and also increased radical
recombination), the oxygen effect is less significant. In some
cases, the oxygen effect can be significantly applied in
radiotherapy (§3.6, section " Physical
and radiobiological factors of radiotherapy ").
Theory of
dual radiation action, molecular-biological theory
Radical theory was later further improved and refined on the
basis of knowledge of molecular biology . Not
only the total energy (dose) transferred to the
tissue is important for the resulting biological effect , but
also the spatial distribution of this energy in
elementary volumes, as well as the time distribution of the dose.
Microdosimetric analysis of the radiation dose distribution and
monitoring of chromosomal aberrations revealed that the radiation
damage of the cell depends on the ionization density
at the critical site. It turned out that to damage the cell it is
necessary to reach a certain critical value of local energy
density at a given place and time (demonstrated
in 1972 by H.H.Rossi and A.M.Keller). Cell
damage occurs through a combination of two
primary events *) taking place on the double strands of DNA
nucleic acid, forming the nucleus of the cell, while the
probability of damage depends on the number of fractures and the
action of repair processes - it is a complex molecular-biological
process.
*) Disruption of only one strand
(DNA) of DNA can usually be easily repaired by the repair
mechanisms of the cell (see below) - this is sublethal
("potentially lethal") damage. Simultaneous damage to
both strands of DNA at nearby sites usually leads to a lethal
effect on the cell. Cellular DNA repair processes do not take
place immediately, but have a certain duration (approximately
tens of minutes). At higher intensity ( dose rate) and
sparsely ionizing radiation, therefore, increases the likelihood
that even a break in the second strand of DNA will occur before
the first strand is repaired, which usually results in lethal
cell damage - individual sublethal damage accumulates in lethal.
The biological effect then depends not only on the total
radiation dose, but also on its time schedule - the so-called dose
rate effect (discussed below in the LQmodel section ) ; at higher dose rates,
a greater radiobiological effect occurs.
![]() |
Schematic comparison of the effects
of beta and alpha radiation on DNA. Above: Beta electrons with a low ionization density cause mostly simple breaks in DNA that the cell can repair. Bottom: Alpha particles with a high ionization density cause double breaks in DNA, which usually result in cell death by apoptosis. |
Particles of "sparsely" ionizing radiation, ie beta and gamma, usually form only one primary disruption (fracture) during their passage through the critical site, so that the final occurrence of damage requires the passage of two individual particles through the site in rapid succession (so-called b - process ) - the number of these damages then depends mainly on the square of the dose , for smaller doses the damage is significantly lower. Particles "dense" ionizing radiation (alpha, neutrons, protons), are capable of a single pass through the critical point cause two or more primary failures (ie. a -Processes ) which is sufficient to create real damage, so the number of lesions, i.e. radiation effect, it is directly proportional to the doseradiation; damage occurs more easily here, these types of radiation have a higher biological efficiency , which reflects the above-mentioned quality factor Q. The mathematical analysis of these processes ( a - and b -processes, as well as processes of cell repair and repopulation) is the so-called linear-quadratic LQ a dose-response model of the radiation effect; is derived and discussed in detail below - the section " Dose - Radiation Effect Relationship ", part of LQmodel .
Chromosome aberrations
Because DNA macromolecules are bound in chromosomes, DNA
damage can manifest itself in changes in the shape,
arrangement and structure of chromosomes - so-called chromosomal
aberrations , which can be observed under a microscope.
A number of different chromosome abnormalities have been
observed, which can be divided into two basic groups :
× Numerical aberrations consisting of an
abnormal number of chromosomes whose intrinsic structure is
intact. They arise during cell division, which can lead to errors
in the separation of chromosomes into daughter cells. This can
lead to polyploidy (multiplication of the whole
chromosome set 3 × or 4 × ) or aneuploidy (numerical
deviation of only a certain specific chromosome, which can be
multiplied 3 × or 4 × , or reduced - 1 × , or
completely lost).
× Structural aberrations , where the
structure of a chromosome is disrupted due to chromosome breaks
(caused by double-stranded DNA breaks) and subsequent
rearrangements. Structural aberrations are divided into balanced
(where the amount of original genetic information is
quantitatively preserved) and unbalanced (where part of
the genetic information is missing or remaining). Several types
of changes in chromosome structure are observed: deletions
(part of the chromosome is missing - either terminal at one end
or interstitial in the middle); duplication (duplication of a section of a chromosome); inversion
(two breaks on one chromosome, rewinding a segment between breaks
and rejoining - the order of genetic information changes); translocation
(exchange of two cleaved segments of two chromosomes); fragmentation
(a chromosome splits into two or more smaller parts); annular
chromosome (deletion of the ends of both arms followed by
twisting and joining of the broken ends); - and several others.
Chromosomal aberrations are most
prominently applied to cell division, where they can either
prevent division or cause uneven distribution of genetic
information into daughter cells. Some chromosomal aberrations are
insignificant and practically harmless, others lead to cell
death, some cause mutations and malformations. Severe and
multiple chromosomal aberrations are observed in tumor cells.
Microscopic (cytogenetic) monitoring of chromosomal aberrations
is also of great importance in the study of the biological
effects of ionizing radiation and in the radiation protection of
exposed persons.
Effects
of radiation on cells
The above-mentioned mechanisms of radiation effects at the
subcellular level result in effects on the basic building blocks
of all living tissues - on cells . When
irradiating a cell with an appropriate dose of radiation, there
are basically two significant types of damage (Fig. 5.2.1 on the
right) :
Thus, irradiation of cells leads to a number of harmful changes ( radiotoxicity ), many of which may be corrected by the body's repair mechanisms, but some may lead to cell destruction and some changes (eg in the DNA code) may be permanent or reproducible. Tissues with intensive cell division, such as hematopoietic or tumorous, mucous membranes, developing fetuses (especially in the early stages of development) are particularly sensitive to the effects of ionizing radiation.
Radiation
effects during the cell cycle
The effect of radiation on cells depends, in addition to the
physicochemical factors mentioned, on the type of cells and on
the time phase in the cell cycle when the
irradiation occurred. Cell division - the cell cycle
The cell cycle is a sequence of
time-ordered processes that a cell goes through in the period
between its divisions - it is the period from
the formation of a cell to the previous division of the mother
cell into two daughters (only very schematically shown in
Fig.5.2.2c). Cycle duration (so - called generation time)
is different for different cell types: for rapidly dividing cells
it is only 20-24 hours, for others it divides only 2 times a year
(eg hepatocytes), some do not divide at all (neurons, lens
cells). The basic division of the cell cycle is the
"resting" period of interphase G
between two divisions (phase G
- English gap ) and phase M
of the cell division itself, mitosis (Greek mitos = thread, fiber ) . More specifically, the cell cycle of eukaryotic cells
is divided into several phases (obr.5.2.2c)
¨ G1 - postmitotic -
after the post-division cells occurs during growth (Eng. Growth = growth) ,
synthesis of RNA, proteins. Physiological processes take place in
a cell, given the type of a particular cell and its function in
the organism. It takes about 10-12 hours.
¨ G0 phase - rest . During the G1 phase,
the cell can leave this phase (and the whole cell cycle) and
enter the resting so-called G0 phase , where it
no longer divides. This is especially true for fully
differentiated cells such as neurons . Some cells are
able to leave the G0 state, go into the G1 phase and start
dividing again if necessary (eg hepatocytes), while the neurons
remain in the G0 state permanently and no longer divide.
¨ S phase - synthetic -
DNA replicates to double the number (duplication of genetic
material). Duration is about 6-10 hours.
¨ The
G2 phase - premitotic - duplicates organelles and forms
the structures needed for cell division. It takes about 2-4
hours.
¨ M phase - mitotic - there is nuclear
division ( karyokinesis ) and then the division of the
whole cell ( cytokinesis ).
The mitotic phase, which lasts about 1-2 hours, is divided into 5
consecutive stages :
× Prophase - a
preparatory phase of karyogenesis, during which the nuclear
membrane dissolves and chromosomes unfold (chromosomes are
doubled after the S-phase, but are still connected in the centromere
). Cytoplasmic microtubules depolymerize and the released tubulin
is used to polymerize three types of new microtubules in the
nucleus: - astral microtubules, diverging radially from
both centrosomes; - polar microtubules , forming a dividing
spindle between the centrosomes ; - kinetochore
microtubules , involved in the pull of split chromosomes to
the poles of the spindle.
× Metaphase - chromosomes line up in the
equatorial plane of the spindle, there is a pull on opposite
sides to the poles of the spindle.
× Anaphase -
chromosomes rupture into two equal parts by shortening the
microtubules of the dividing spindle.
× Telophase -
the dividing spindle disappears, chromosomes are concentrated in
two new nuclei, around which a nuclear membrane is formed. This
completes karyogenesis.
× Cytokinesis -
a cytoplasmic barrier is formed between the two parts. This
occurs either by strangulation due to the contractile ring
(in animal cells); in yeast it is budding, in plant cells a
compartment between the cells grows from the center to the edge.
The mother cell is
thus divided into two identical daughter cells
*), which enter the G1 phase; ® cycle repeats - if not stopped by the
check nodes (described below), especially physiologically
restriction G1 Checkpoint when the cell is
"service" G0 phase, further Sunday and conducts
differentiated function ..
Considerably simpler manner undergoing division prokaryotic
cells (bacteria): it is binary division , in
which the cell first elongates into an elongated shape,
replicates its DNA, begins to form a septum in the middle,
whereby the mother cell then splits into two identical daughter
cells.
* ) Stem and effector
cells
In multicellular organisms with different differentiated tissues,
the mechanism of division is more complex. Here, the tissues
consist of stem cells (maternal, clonogenic) and
daughter, effector cells . Stem cells are
capable of unlimited division, while they are able to produce
both identical stem cells and daughter cells, bearing the
properties of a given differentiated tissue - asymmetric
divisionto two different cells, an identical stem cell
and a different daughter cell. Due to their division, clonogenic
stem cells are more radiation-sensitive than
daughter effector cells (which, in addition, are continuously
replenished by stem cell division).
Asymmetric division ensures the process of differentiation
, in which cells, by their structure and function, adapt to the
specific role they are to play in the organism. All cells in the
body are equipped with the same genetic equipment, but as a
result of this process, only a certain part of the genetic
information is realized in a particular cell (due to specific transcription
factors only certain genes are transcribed in the cell, others
are not applied). Daughter effector cells usually enter the
quiescent G0 phase of the cell cycle.
Cell
cycle control nodes
The complex process of cell
division is controlled by several stages of
regulation. The key points of the cell cycle are certain " check
nodes " or points ( Check Point), in which
the state of the cell in a given phase and its ability to
continue the cycle is "evaluated" (Fig. 5.2.2c). In the
control nodes, it is verified whether all events taking place in
the respective phase of the cell cycle have been successfully
completed - before the cell proceeds to the next stage of its
cycle. The main role of checkpoints is to "supervise"
the correctness or damage of DNA to ensure proper cell division
with maximum flawless transmission of genetic information
. Certain control mechanisms probably work continuously at every
moment of the cell cycle, but their activity results in several
significant milestones of individual stages :
Y First checkpoint G1 ( G1-checkpoint ) or G1 / S is at the end of the G1 phase. Here it is
decided whether the cell will continue the division cycle or go
into the resting G0 phase. Control node G1 is sometimes also
called start (only from this point a
new cell cycle can continue) or restriction
- it forms a kind of "barrier" to the continuation of
the cycle, which is overcome by the expression of cyclin D
induced by growth factors; otherwise, the cell remains in the G0
resting phase.
Y The second control node is in S-phase
and controls DNA transcription; suspends the cell cycle until the
DNA is completely replicated. Y
Third G2 / M checkpoint , located at
the end of phase G2 ( G2-checkpoint
) controls a number of factors that determine whether a cell is
ready to successfully enter mitosis. It oversees the integrity of
DNA, examines whether DNA is damaged and whether its synthesis
has been completed, delays the onset of mitosis, and stops the
cell cycle in the event of DNA damage.
Y The last control node M ( M-checkpoint
) comes into play only during mitaphase in anaphase and
checks the correct course and termination of mitosis. The
signaling pathway of the mitotic control node M checks, among
other things, the correct connection of the chromosome
kinetochore to the dividing spindle. If the control mechanisms
find an inconsistency in one of the control nodes, the cell cycle
is interrupted: either repair processes are
started
, or in the case of more severe
irreparable damage (such as a double DNA break), apoptosis
will begin (Fig. 5.2.2c in the middle) - "programmed"
cell death described in more detail below.
Radiosensitivity of cells and tissues
The greatest radiosensitivity is manifested when the cell is
affected in the late G1 and premitotic G2 phase, when checkpoint
mechanisms can stop the cell cycle. Slightly lower sensitivity is
in the M phase and in the transition between the G1 and S phases,
the lowest sensitivity for cells in the G0 phase.
Living tissue is made up of a mixture of
cells at various stages of the cell cycle. The average time that
cells are in certain phases depends on the type of tissue.
Tissues growing rapidly with a short cell cycle
have a higher time proportion of G2 and M cell phases, so they
are more sensitive to
radiation. Slow-growing well-differentiated
tissues (such as nerve, muscle, ligament) are relatively radioresistant
, as most cells remain in the G1 phase for a relatively long time
and some are even in the G0 resting phase. Different radiation
sensitivities of individual tissue types are important from the
point of view of radiation protection and play a
key role in radiation therapy in radiotherapy ( §3.6 " Radiotherapy " ), where fractional
irradiation and sometimes a combination of chemotherapy and
radiotherapy are used, inter alia to achieve some cell cycle
synchronization with irradiation cycle.
Radiation damage ~ Þ poisoning of the organism with
chemical poison
From the above description of the mechanism of the harmful effect
of ionizing radiation on living tissue, it follows that the
radiation effects are not "mysterious" unusual
phenomena caused by invisible radiation. The end effect is chemical
or chemical-biological: the radiation only supplies energy
to the tissue (in a specific form of ionization), which
ultimately leads to the production of " poison
" (free radicals) and internal chemical
" poisoning " of cells - we are
talking about radiotoxicity . After all, it is
similar to diffusingly applying, for example, hydrogen peroxide
or another to the tissue a highly reactive chemical
having denaturing or genotoxic effects. There
are three characteristic differences between chemical poisoning
and radiotoxicity :
1. Chemical poison molecules are delivered to the tissue from
the outside , they penetrate the metabolic pathway
(blood, lymphatic), they accumulate inhomogeneously in certain
cell types. Ionizing radiation supplies only energy and toxic
substances are generated inside cells and
tissues, while they are distributed practically homogeneously
in the entire volume of irradiated tissue, inside all cells. The situation is more complicated by internal
contamination with a radioactive substance when its
distribution is inhomogeneous - in the target tissues and organs,
depending on the chemical composition. And also for short-range
radiation in the tissue ( a,
b ), when only the immediate vicinity of
the interaction site is irradiated.
2. Difference in the nature of the dose-response
effect . When lower concentrations of chemical toxicants
are applied, almost all cells survive, and only when a certain
threshold concentration is exceeded will practically all cells in
the population die. When exposed to ionizing radiation, even
small doses can result in the destruction of a small percentage
of cells, but even after receiving very high doses, a certain
part of the cell population survives (see "LQ model"
below). The radiobiological effect has a statistical probabilistic
character, it is governed Poisson distribution *) of
probability. After irradiation of a set of N 0 cells, N cells
survive, with N / N 0 ~ e - (number of lethal lesions) . This dependence is mathematically realized in a
linear-quadratic model, derived below.
*) The Poisson distribution generally
models random events in a set of a large number of elements in a
situation where the probability of a given process is relatively
small with respect to the total number of elements. If we have a
set of elements (atoms, cells) with instantaneous number N
, in which the given stochastic process (nuclear decay,
cell damage) is caused by the control factor f
(time, dose) with probability l
, then the element of the factor D f causes the loss
of the members of the set by D
N = - l
. D f elements. This leads to a differential equation for
the dependence of the number of remaining elements N on
the acting factor f : dN / df = - l , the solution of which
under the boundary initial conditions N (f = 0) = N o is an exponential
function N = N o .e - l .
f . It is derived and discussed in
more detail in §1.2, part " General laws of atomic nucleus
transformation " for the case of
radioactive decay.
3. Another difference in DNA damage caused by common
factors (such as oxidants from metabolism) and ionizing radiation
is that after ionizing irradiation, clusters of
DNA damage increase (especially in densely
ionizing radiation); for common non-radiation damage, this
distribution is more even.
Repair
processes
Cells are not completely defenseless against radiation damage;
when irradiating living tissue, there are not only one-way and
irreversible changes leading to damage to cellular structures and
their functions. In the biological stage of the radiation effect,
there are also opposing processes - processes of repair
and regeneration , which lead to the restoration
of the ability of cell division and function of tissues
and organs. Thus, radiation changes in living tissues may be reversible
.
In the early stages
of evolution, cells lived under the influence of shortwave
radiation, especially ultraviolet radiation. During evolution,
mechanisms have had to evolve that maintain the integrity of DNA
(relative stability of genetic information). Enzymatic repair
systems, which are able to eliminate DNA damage (radiation or
chemically induced), have been a positive evolutionary
factor for cells and have mostly been preserved
in cells. It is also worth mentioning the fact that repair
systems are not closely specific to only one pollutant.
There are basically two types of repair
processes at two different levels :
After a specific "radiation
action" (cell intervention by a quantum of ionizing
radiation), the probability of a biological effect depends mainly
on two circumstances :
1. The type of DNA
damage (Fig. 5.2.2b). 2. The phase
of the cell cycle in which the damage occurred (Fig.
5.2.2c).
Simple breaks of DNA strands can usually repair repair mechanisms
flawlessly (if they have "enough time" to do so).
Double DNA breaks, if they occur in the G1 and G2 phases, are
recognized in the "check points" and usually lead to
cell death (Fig. 5.2.2c in the middle). However, DNA damage that
occurs after the "checkpoints" stage may not be
recognized by cellular regulatory mechanisms and may lead to
mitosis - there is an increased risk of dividing cells with
altered genomes, which may result in mutations (stochastic
effects) - fig. 5.2.2c below. During the practical irradiation of
the organism, the individual cells in the tissues are in various
phases of their cell cycle and at the same time DNA of various
kinds is damaged. Therefore, on average, individual microscopic
events consist of a final radiobiological effect - deterministic
or stochastic.
The speed of the cell cycle also depends
significantly. Cells that divide rapidly have, on average, less
time to repair damage to their DNA, so they will suffer more from
the consequences of unrepaired or incorrectly repaired damage.
This leads to an important general conclusion: rapidly
dividing cells are more radiosensitive .
The repair and regeneration processes
lead, inter alia, to dividing the dose into smaller sub-doses at
sufficient time intervals leading to smaller biological effects
compared to the same dose absorbed in a single dose. Resp. at the
same total absorbed dose, the biological effect decreases if it
was achieved at a lower dose rate (which of course corresponds to
a longer exposure time) - see "LQ model" below - dose
rate effect .
Effects of radiation at the tissue level
The effects of radiation at the subcellular and cellular levels
discussed above are the basic starting point for
understanding the effects at higher levels of the organization -
in tissues, organs, the whole body. However, they are not a
sufficient way out! There is a well-known general experience that
a system is not just a simple sum of its elements (or "an organized whole is more than the sum of
its parts ") . Some radiation
effects in living tissue are caused not only by basic cellular
mechanisms, but also by the interaction of
various tissue factors, such as intracellular
communication. biochemical signaling pathways, movement
of molecules and ions through the intercellular space, cell
division and tissue regeneration. At the level of organs and the
whole organism, complex biological relationships between
different types of cells and tissues in the activity of organs
and functional relationships between individual organs in the
body approach this.
Biochemical
interactions of cells. Extra-target remote-induced radiation
effects - bystander effect, abscopic effect
The view of classical radiobiology
is largely mechanistic : damage occurs only
in cells that are affected by ionizing radiation or a chemical
agent, which damages the DNA or other important structure of the
cell . This is indeed the case when irradiating a set of
isolated cells (such as bacterial colonies).
However, in higher organisms, cells are incorporated into tissues
in which cells biochemically interact with each
other through a number of complex processes
(especially regulatory ones). Some of these processes ( repopulation,
redistribution, reoxygenation ) are mentioned below in
connection with the dependence of biological effects on the
radiation dose and its time course. Due to these cell
interactions, it can be expected that other surrounding cells in
the tissue may react to (radical) damage to one
particular cell in a certain way .
This process has actually been observed in
experiments with very narrow sharply collimated beams ( micro-beam
) radiation a which irradiated cells in
tissue culture. It was found that after irradiation of the target
cells, the surrounding cells showed signs of damage
, even though they were not irradiated
themselves . Experiments in which a sample of irradiated cells
was transferred to a colony of unirradiated cells led to similar
results. This remarkable effect could be due to the mentioned
biochemical interactions of cells in the tissue. The exact
mechanism of this phenomenon is not yet known. The surrounding
cells could be affected in basically three ways :
× Through the intercellular environment
Cells affected by radiation can produce certain diffusible
substances
that are able to affect other neighboring cells. Primary
irradiated and lethally damaged cells can "send chemical
signals" to their surroundings ( extracellular matrix
) - release biochemical molecules involved in apoptosis of
irreversibly damaged irradiated cells (p53 protein or TRAIL
ligand is considered, as mentioned in the passage above)
Apoptosis "), or molecules of toxic, oxygen or nitrogen
radicals. These substances can diffuse and enter surrounding
cells (or bind to appropriate receptors on the surface, activate
external apoptosis signaling pathways), in which they can cause a
similar response to that of a directly affected cell.
× Over intercellular junction
Intercellular communication ( gap
junction ) they are carried out by
membrane channels, called connexons , with a diameter of
about 1.5-2 namometers, through which molecules up to 2 kDa can
pass. When one cell is damaged, the canal usually closes quickly,
preventing damage to neighboring cells. However, if this pathway
is not inhibited in time, damage can be transmitted to
surrounding cells.
× Macrophages
Finally, the activity of macrophages could contribute to
the apoptosis of the surrounding unaffected cells , which, in
addition to the apoptotic cell itself, can also attack some
neighboring cells.
![]() |
Bystander effect. Radiation damage to a single cell can induce damage to some surrounding cells that have not been irradiated. |
To this effect radiation effects induced
in neighboring cells is used to name the
bystander effect (Eng. Bystander
= viewer, bystanders, gaper) - " effect
bystander viewer": surrounding directly the unaffected
cells are not "neutral observers" radiation damage of
irradiated cells, but are also "drawn" into this
process. The bystander effect thus slightly increases the
total number of radiation-damaged cells in the irradiated tissue
(Fig. 5.2.4b). The bystander effect can cause apoptosis
, chromosomal aberrations and mutations
in surrounding cells .
Note: The
bystander effect was observed not only in radiation-damaged
cells, but also in local chemical cytotoxic damage.
Abscopal effect
The phenomenon of biological changes in the non-irradiated part
of the biological system as a result of the reaction of the
irradiated part is generally referred to as a side
, extra-target or abscopic effect (lat. Ab = outside, away; scopium = target, target,
angle of view ) . Post-radiation
changes usually occur in cells and tissues closely adjacent to
irradiated areas - such as the aforementioned bystander
effect . However, " long-distance
" abscopic effects were also observed . In
radiotherapy with local irradiation of a single tumor lesion
sometimes (unfortunately rarely) an immunoeffect - immunogenic cell
death - is also induced against other metastases of the same tumor (see also §3.6, section " Immunotherapy ") . The exact mechanism of
the aboscopic immunoefect is not yet known, but it is probably
due to massive apoptosis or necrotic death of tumor cells
irradiated with a high radiation dose. This elicits a local
inflammatory immune response in which T
cells form within the irradiated tumor , which can be specifically
activated by the uptake of antigens from tumor cells.
These specifically activated effector T cells then migrate
to unirradiated secondary tumors, where they initiate targeteda
"killing" immune response against tumor cells of a
given type that have the same antigens (involving monocytes
transforming into macrophages).
In
addition to this highly desirable effect, an adverse abrosive
effect in normal healthy tissues that could induce genomic
instability, cell death, or oncogenic cell transformation is
sometimes discussed . However, such a mechanism has not been
demonstrated, the causes of the side effects of radiation on
healthy tissue are probably different (§3.6, section " Side effects of radiotherapy -
radiotoxicity, secondary malignancy
"). It would be unlikely if the radiation-mutated cells
merely migrated and established a distant tumor site without such
a site forming near the irradiated site.
However, a situation could arise where the irradiation
causes a decrease in the body's immunity, as a result of which a
still "dormant" clone of mutated cells may initiate
tumor growth at some point. Such a complex process, however,
probably not be considered abskopální radiation effect ..? ..
Any radiosensitivity
of cells and tissues
organism is a functional complex tissues and organs that have the
same sensitivity to irradiation (radiosensitivity). At the same
absorbed dose, different biological effects are seen in different
tissues. In analyzing the effects of radiation on cells, we found
that rapidly dividing cells are more sensitive to radiation
damage. This basic knowledge is also manifested at the tissue
level and is sometimes expressed by the rule: "the radiosensitivity
of the tissue is directly proportional to the reproductive
activity and indirectly proportional to the degree of
differentiation" *). This rule is only approximate,
for specific tissues and organs it is approached by specific
biological effects (see below " Local tissue and organ radiation effects ") . Tissues and organs have
different sensitivities not only to damage by cell death, but
also different susceptibility to application of cytogenetic
effects, the risk of cancer.
*) The direct and inverse There
can not be taken mathematically, but only as an expression of the
increasing or decreasing trend. This is called ever rule Bergonia-Tribondeau
, according to the first authors who came to him empirically
arrived.
Relationship
between dose and biological effect
Of course, the biological effect of radiation is primarily
dependent on the size of the absorbed dose, that it increases
with dose. In terms of dose-effect relationship, we distinguish
between two basic types of radiobiological effects :
For stochastic effects, the
severity of the disease and the course of the disease do
not depend on the dose ; only the probability of
tumor or genetic damage depends on the absorbed dose . These are
disease states which, even without the influence of radiation,
occur " spontaneously ", without an
obvious cause *) in the population. In individual cases, it is
not possible to distinguish radiation-induced tumors and genetic
changes from spontaneous cases, their clinical picture is the same
(there are no symptoms specific for tumors
caused by ionizing radiation) . Ionizing
radiation only increases the likelihood of these
diseases, the corresponding risk is additionalto other
risks. The average risk factor for radiation-induced
malignancy is estimated at 0.055 Sv -1 , or 5.5% per 1Sv (ie if 1000
people receive an effective dose of 1Sv, 55 of them can be
expected to cause fatal cancer) .
*) As discussed above, this is
probably due to the enotoxicity of some chemicals
, which either enter the cells from the outside (through the
body's metabolic pathway) or are formed inside the cells (during
the internal metabolism of the cells). These substances enter the
nucleus, react with DNA and cause disorders of its gene sequence,
which may not be successfully repaired ...
Dependence
of stochastic effects on age
At the same radiation dose, the probability
of stochastic effects is inversely related to the age of
the irradiated individual. This is due to two
circumstances :
¨ Time factor - stochastic radiation
effects have a long latency, the probability of their
manifestation increases with time since irradiation. When the
body is irradiated at a younger age, there is probably more time
available for late stochastic effects to occur. When irradiated
in old age, stochastic effects are often not enough to apply
until the end of life.
¨ In children , due to growth, there is a
more intense cell division, which leads to higher
radiosensitivity.
Linear-quadratic dose dependence of stochastic effects
According to the theory of dual radiation action
is the probability of radiation damage to the cell - and thus the
probability of unsuccessful DNA ® repair - the probability
of mutations and the occurrence of stochastic effects, especially
malignant transformations, depending on the ionization
density at a given site. Similar to deterministic
effects (where radiation cell killing has a linear-quadratic dose
dependence - see the " LQ model " for derivation
below ), so for stochastic effects, the probability distribution
of malignant transformations at an effective dose is linear-quadratic
. At low doses up to about 1Sv, the curve is linear the
shape is directly proportional to the frequency of malignancies
at the dose (black line in Fig. 5.2.3a), at higher doses the
occurrence of radiation-induced malignancies is proportional to
the square of the effective dose - quadratic dependence.
However, the theoretically expected quadratic dependence of
stochastic effects for higher doses is difficult to demonstrate,
given that at high doses almost all cells in the population die
rapidly with deterministic effects.
Thus, at low doses,
for stochastic effects, it is usually assumed that the degree of
effect, ie the probability of radiation-induced damage (tumor or genetic) is linearly
dose-dependent (black line in Fig. 5.2.3a) and that the
stochastic effects are non-threshold - they can
be caused even by very small doses, even at the level of the
natural radiation background, although with a slight probability.
In classical radiobiology, it is hypothetically assumed that each
mutation of an individual cell (whether generated by radiation or biochemically) can be the first step to carcinogenesis
(it is discussed in §3.6 " Radiotherapy ") . Even if this were the
case, however, the mutagenic effects of very low radiation doses
may be questionable ..? .. - will be discussed below.
Note: In
the interest of scientific objectivity, it would
perhaps be appropriate to point out at this point that in the
area of ??very low doses <0.2 Gy, the generally accepted
linear threshold-free dependence is only a hypothesis.,
resulting from the direct extrapolation of proven effects from
higher dose areas (> 0.5Gy) towards zero, to the low dose
range, where these effects have never been directly demonstrated
(discussed in more detail below in the
section " Small doses of radiation: - are
harmful or beneficial? ")
.
The " conservative
approach " to radiation protection is based on this
assumption, the so-called linear threshold-free
dependence of stochastic effects, which is reflected in
a number of standards and regulations for working with ionizing
radiation. However, recent radiobiological studies indicate that
the dose-response of stochastic effects is not linear, but that
at very low doses the effects are likely to be lower.
than would correspond to the linear dependence *) - blue curve in
Fig.5.2.3a.
*) This behavior could be
related to radiation-induced repair and also to
the so-called hyper-radiosensitivity to low doses (see below "Deviations from the LQ model") , when irradiated cells (with the risk of altered
genome) are more likely to die. The views of radiobiologists
differ here, and the relatively increased probability of
low-dose stochastic effects is sometimes discussed , eg in
connection with the afore mentioned bystander effect ..?
..
In addition, if some alternative
views are confirmed (mentioned
below " Small doses of radiation: - are they harmful
or beneficial? "), in fact, the curve of the dependence of stochastic
effects on the radiation dose could have the shape of a green
curve in Fig. 5.2.3a - even for stochastic effects there would be
a threshold (!) (similar
to deterministic effects) , but many times
lower. And at the lowest doses, the so-called radiation
hormesis could manifest itself - a section of the green
curve of the curve below the horizontal axis ..? .. At present, there
is no direct evidence that low levels of radiation are
harmful to health (see the discussion below
in the section " Small doses of radiation: - are
they harmful or beneficial?
").
Fig.5.2.3. Dependence of biological effect
on the size of absorbed radiation dose.
a) Probability of occurrence for stochastic
effects. b) Severity of damage for deterministic
effects.
c) Dose dependence of the surviving fraction of N / N 0 cells according to a
linear-quadratic model.
Deterministic effects become
clinically manifest until after a certain threshold dose
, while with increasing dose increases the probability of damage (i.e. when irradiated group of people growing number of
individuals, which can damage demonstrated, at higher doses the
effects are in each) and also at the severity
of the damage increases . The dependence of the
radiation effect on the absorbed dose for deterministic effects
is shown in Fig. 5.2.3 in the middle. The basic pathogenic
mechanism is a reduction in the number of cells
( cell depletion ) in the irradiated tissue. Toxic
substances also contribute to the harmful effect,
arising from the extinction and decomposition of a large number
of cells. The S-shaped shape of the curve, starting from a
certain dose threshold, is a reflection of the fact that there is
a certain functional reserve in the irradiated
tissue (cell population) , usually quite large. Therefore, a
decrease in the number of cells with increasing dose does not
initially cause any functional problems in the irradiated tissue,
only at higher doses does the deficit of cells
lead to somatic manifestations. The value of the threshold dose
for humans around 1Gy according to Fig. 5.2.3b
is only average ( whole body ) and
indicative. Each tissue generally has a different
threshold dose of deterministic effects, depending on cell
radiosensitivity and functional reservein the
tissue - eg approximately: skin 3Gy, lungs 5Gy, sperm 0.3Gy, eye
lens 1.5Gy, developing embryo in utero 0.1Gy, .....
Pathologically
increased radiosensitivity
occurs in individuals with genetic disorder of chromosomal
instability , where the ability of repair
mechanisms at the cellular level is reduced (impairment of
stability and reparability of DNA by homologous recombination -
hypersensitivity to genotoxic effects), as well as reduction of
immune processes (immunosuppression) at the organism level *). If
both dominant genes are OK in a heterozygous cell,
radiation or other damage to one of them may not impair cell
function. However, if one gene is OK and the other is disrupted,
damage to one gene can lead to total cell dysfunction. In homozygotes
with such a reparability disorder, the consequences of the damage
are even more pronounced, they are fully applied. In these
individuals, the threshold dose is reduced for
deterministic effects, and even diagnostic irradiation (eg more
demanding X-ray examination of CT or angio, dose approx. 40-60
mSv) can cause mild deterministic effects. Radiotherapy
shows increased radiotoxicity to healthy tissues,
chemotherapy increases sensitivity to cytostatics .
Also, the risk of stochastic effects, even from the
natural radiation background or other pollutants (chemical,
including metabolic products), is significantly higher - more
frequent occurrence of cancer (especially lymphomas).
*) One of such disorders is the so-calledNijmegen
breakage syndrome (NBS, the name is derived from a city in
the Netherlands, where the disorder was first identified in 1981
and where there is a central registry of these patients) -
autosomal inherited syndrome of chromosomal instability. It is
caused by a mutation in a gene called NBS1 or NBN
, which encodes the protein nibrin , which has an
important function in repairing chromosomal breaks caused by
ionizing radiation or other genotoxic agents. Genetic chromosomal
instability also occurs in Ataxia telangiectasia
syndromes , Bloom's syndrome , Fanconi anemia,
Xeroderma pigmentosum , Li-Fraumeni syndromemutated
TP53 gene encoding p53, or the very rare Werner
premature aging syndrome . A number of pathological
clinical manifestations result from cell cycle disorders. In
addition to increased radiosensitivity and more frequent
occurrence of cancer, there are also growth disorders,
neurological and skin manifestations, and infectious diseases
often occur due to reduced immunity. Fortunately, these
congenital inherited disorders, which are not causally treatable
(only their specific clinical manifestations can be treated),
occur very rarely, the total incidence of all mentioned species
is about 0.02% of the population. However, there are
significantly more heterozygous carriers, about 0.5%.
Warning: Please
do not confuse this pathologically increased overall
radiosensitivity with physiological hyper-radiosensitivity
(relative) in the area of ??low radiation doses, which is
inherent in all cells - is discussed below in the section " Hyperradiosensitivity
to low doses. Model of induced repair ".
Deterministic
+ stochastic effects
The stochastic and deterministic
effects of radiation have basic intracellular mechanisms and some
external aspects in common and cannot always be strictly
separated from each other. The basis of deterministic
effects lies in the mechanism of radiation killing of
cells , which has a probabilistic (ie
"stochastic") character at the cellular level, is
governed by Poisson statistics (see below " LQ
model"). At medium and higher doses, however, the
number of killed cells is so large that statistical fluctuations
are practically non-existent, the resulting dependence is deterministic
. Even at low doses (below the threshold of deterministic
effects), for which only stochastic effects are usually
discussed, a small number of cells are "secretly"
killed, not only because the remaining intact cells are
sufficient to provide a functional need for tissue or organ and
are replaced in time by the division of these intact cells.The LQ
model not only describes deterministic radiobiological effects,
but also implicitly lies in the foundations of probability of
stochastic effects.
It should also be borne in mind that, along with the
early deterministic effects are latent and may applylate
stochastic effects if the organism survives
deterministic effects. This is observed with radiotherapy based
on deterministic effects on tumor tissue, where in addition to
acute radiotoxicity, secondary post -radiation malignancies
may occur over time , due to the stochastic effects of the part
of the radiation absorbed outside the primary target tumor
(including scattered radiation) and irradiated. other tissues and
organs (§3.6 "Radiotherapy", part " Physical and
radiobiological factors of radiotherapy ").
Terminological note:
In the following text we often use the term " deterministic
radiation effect " in a somewhat weaker and more
general meaning - in the sense of lethal damage and cell
death, without the need for the manifestation of somatic
manifestations for the whole organism. Thus, "deterministic
effects at the cellular level."
Comparison of the nature of deterministic and stochastic effects of radiation on the organism |
Properties: | Deterministic effects | Stochastic effects |
Pathogenesis: | Cell death - reducing their number | Change of cytogenetic information - mutations |
Specificity: | Specific clinical picture, typical for the effects of ionization. radiation |
Non-specific image, indistinguishable from spontaneous cases |
Dose dependence: | The effect only becomes apparent from
a certain threshold dose, then increases with dose |
The probability of occurrence
increases with dose from zero (threshold-free dependence) |
Time dependence: | Mostly relatively fast onset | Late effects, long latency |
Radiobiological modeling
The radiobiological
effects of radiation on cells and tissues generally
depend mainly on the absorbed dose, on the type of radiation, the
type of cells in the tissue and also on time factors. These
generally complex dependencies have been measured in a number of
radiobiological experiments and verified in clinical studies,
especially in radiotherapy. There was a natural attempt to
describe these empirical laws using mathematical models
and functions that would express the dependence of the
radiobiological response on dose D , its time distribution
and the properties of irradiated tissue. Models that would allow
to compare and analyze different radiobiological data and predict
cell survival based on physical aspects (type
and energy of quantum radiation) and biological
properties of cells and tissues (radiosensitivity,
repair capabilities of normal and tumor cell lines).
It is mainly a functional expression
of the surviving number of N cells from the
originally irradiated number N 0 , resp. dose dependence of the surviving cell
fraction [N / N 0 ] (D). Until the 1970s, this modeling consisted in the
construction of empirical mathematical functions
containing appropriate powers of dose D , irradiation time
T and number of fractions n (powers
were mostly non-integer, eg T 0.33 or T 0.11
, n 0.24etc. - so did M. Standquist in 1946, or F.
Ellis in 1969) ; these functions were
interspersed with empirically determined dependencies.
A major advance in radiobiological
modeling occurred in the 1980s, when a so-called linear-quadratic
(LQ) model was formulated on the basis of more detailed
microdosimetric measurements and evaluation of chromosomal
aberrations - see below. This approach is no longer purely
empirical, but is based on an analysis of the mechanisms
of the process of damage and killing of cells by
ionizing radiation at the subcellular and molecular level. The
parameters of this model (coefficients a, b and time factors) can be
derived from the measured data (experimental and clinical), which
allows within one modeldistinguish the behavior
and responses of different tissue types. The LQ model is used
primarily for deterministic radiation effects, but implicitly
lies in the basis of stochastic effects. We will analyze the LQ
model in more detail here, then briefly list some other models
below.
Linear-quadratic
(LQ) model of radiobiological effect
The deterministic radiation effect, consisting in the destruction
of a larger number of cells, is caused mainly by the
breakage of both strands of DNA in the nuclei of cells.
As discussed above (see " Intervention
and Radical Theory of Radiation Effect ") , according to the theory of dual radiation action
, radiation damage to a cell depends on the ionization
density at a critical site. To determine the functional
expression of the surviving number of N cells (from the
originally irradiated number of N 0 cells ) on the received dose D , the LQ model
uses three initial assumptions :
× The
break of a single strand of DNA can be easily repaired -
sublethal damage ® cell survival.
× The break of both strands (strands) of DNA is difficult
to repair - lethal damage ® usually cell death (apoptosis).
× These are probabilistic events
with Poisson statistics: after irradiation of a set of N 0 cells, N cells
survive , where N = N 0 .e - <probability of lethal cell damage> .
Double DNA break can be caused by two types of
processes :
¨ a -process - intervention of one ionizing
particle, which breaks both strands-strands of DNA at the same
time (manifests itself mainly in densely ionizing radiation, but
also in sparse ionizing radiation secondary electrons can damage
both branches of DNA) . The number of irreversibly damaged cells
is directly proportional to the dose - a linear
dependence on the dose D. If the initial number of cells is N 0 , then after
irradiation the number of surviving cells can be expressed by the
exponential relationship N = N 0 .e -a .D , where a is average
probability a-damage per unit dose (derivation from Poisson's
statistical distribution is analogous to the exponential law of
radioactive decay - see §2.2, section " General laws of atomic nucleus
transformation ", instead of time t
would be dose D ). Coefficient values a range from about
0.1 ¸ 0.8
Gy -1 .
¨ b -process - time-close interventions of
two independent ionizing quanta, in which each of them breaks one
strand of DNA (breaking one strand of DNA allows repair - sublethal
damage, damage to both strands is usually lethal
). The number of radiation-damaged cells here is proportional to
the square of the dose - quadratic dependence on
dose D. The relevant exponential law of cell number decrease in
this case will be N = N 0 .e -b .D 2 , where b is the average probability of b -damage per square unit
benefits. The dependence is initially gradual, almost linear
(possibility of cell repair after sublethal damage), then turns
into a steeper exponential course, caused by the accumulation of
sublethal effects in lethal. The coefficient b acquires values of
about 0.01 ¸ 0.1 Gy -2 for human cells .
The total probability of cell survival when applying
both processes will then be given by the product of individual
probabilities, which leads to the resulting exponential law: N =
N 0 .e - ( a .D
+ b .D 2 ) . The dose dependence of cell survival is often
expressed by the curve of the surviving fraction of
cells N / N 0 on a (semi) logarithmic scale:
-ln (N / N 0 ) = a .D + b .D 2 - linear-quadratic
dependence, Fig.5.2 .3c above.
For densely ionizing radiation (high LET, mainly a-process) this
curve has an almost linear shape , for sparsely
ionizing radiation (low LET, b
-process predominates
) the graph has the shape of a parabola .
In LQ model applications, an a/b
ratio [Gy] is often introduced to express the
dose at which the damage by the a -mechanism is the same as
the b -mechanism
(the linear and quadratic components are biologically equivalent
in terms of the resulting lethal effect for cells). Graphically,
the value of the ratio a / b characterizes the curvature of the graph of the
dependence of the surviving fraction of cells ln (N / N 0 ) on the dose
according to Fig. 5.2.3c. Values a / b they depend on
the relative representation of the individual phases of the cell
cycle. For rapidly dividing cells (eg tumor cells) the values
??of the ratio are a / b » 10 Gy, for normal (late-reacting) tissues the a / b is» 2 ¸ 4 Gy. The a / b ratio appears
in the derived biophysical dose quantity, which is the so-called biologically
effective dose ( biological dose equivalent )
BED º -ln
(N / N 0 )
/ a =
D. [1 + D / ( a / b )]. BED is important in radiotherapy in
assessing the effect of fractionation of the total
radiation dose D on nsub fractions d , where
BED = D. [1 + d / ( a / b )] (see §3.6 " Radiotherapy ", section
" Physical and radiobiological
factors of radiotherapy
") .
Time factor
Such simple dependences apply in the case
of a single irradiation . In the case of time- prolonged
irradiation - continuous or repeated (fractionated), in
addition to the mentioned mechanisms, time factors of
cell repair (especially in the case of b- damage) and repopulation
of cells by division in tissue also apply. When
irradiated with dose D during the irradiation time T in the LQ model, two additional
quantities are introduced into the initial linear-quadratic
dependence - factors of cell regeneration RG and
repopulation RP :
1. Reparation
For each elementary time interval D t, during which the cells
receive a dose D D = D. D t / T, and damaged while N. b . D D 2 cells, at the same time it is enough to regenerate N. l . D t cells, where
parameter l is the rate of cell repair ( l = ln2 / T 1/2 , where T 1/2 is the half-life
of repair). Integration from 0 to T gives a modified
exponential law N = N 0 .e - RG. b
.D 2 , in which an additional regeneration time coefficient,
the so-called Lea-Catchesid factor *) RG = 2[(1-e
- l .T ). (1-1 / l .T)] / l .T, appears for the quadratic exponent , which is a
function of the rate of cell repair l and irradiation time T. The
rate coefficient of repair l ranges from about 0.4 hours -1 for normal tissues to about 1.5 hours -1 for rapidly dividing
tissues (e.g. tumor).
*) Lea-Catcheside dose-time integral:
In general, continuous irradiation of a set of N
(t) cells with a time-varying dose D (t) with an instantaneous
dose rate R (t) = dD (t) / dt can be considered. Then, for each
elementary time intervalDt during which the cells receive a doseDD = R (t). Dt and N (t) is
damaged. b. DD 2 cells (sublethal), at the same time it is enough to
regenerate N (t). l. Dt of cells, where parameterlis the rate of cell repair.
By integrating the relevant differential equation from t = 0 to
the continuous time t , under boundary conditions at t = 0
N (0) = N0
, we obtain a solution for the time dependence of the number of
cells N (t), which can also be written in the original
(quadratically) exponential form N (t) = N 0 .e - RG (t). b
.D (t) 2 , where the modifying quantity
RG (t, l ) = [2 / D (t) 2 ] . 0 ò t
R (t) .dt . 0 ò T
' R (t'). E - l .
(T-t ') dt'
is the so-called generalized. Lea-Catchesid function (a function of this kind in the years 1942 to 1945 have
found empirically D.E.Lea and D.G.Catcheside
when examining cell aberrations on Drosophile ) , expressing the "balance" between cell damage
by dose rate R (t) and their continuous repair with a rate
coefficient of l . The RG function depends on the time course of
the dose rate R (t) during the entire exposure. In extreme cases
of short exposure time T << 1 / l is RG ® 1 (repair does
not apply during irradiation), otherwise long irradiation
time T >> 1 / l
is RG ®
0 (almost all potentially lethal damage can
be repaired) .
b -process, in
co-production with cell repair, thus causes the so-called dose
rate effect: that the biological effect of ionizing
radiation depends not only on the total absorbed dose, but also
on the dose rate *), as is schematically shown
in the lower part of Fig. 5.2.3c. For low dose rate
(LDR), the number of reparations is high and the curve of the
surviving fraction of cells is relatively flat - less
biological effect (blue curve). The higher the dose
rate, the more likely it is that a break in the second strand of
DNA will occur before the first strand is repaired, usually
causing lethal damage to the cells. For high dose rate
(HDR), therefore, the curve of the surviving fraction is steeper
- a larger biological effect , significantly
increasing with dose (red curve in Fig. 5.2.3c below).
*) In the exponential law for b -process N = N o .e - RG.
b .D 2 exits dose rate explicitly when a
quadrate dose D 2 = DD single dose quantity D we transfer to
Lea-Catchesidova factor RG : RG .D = 2. [(1-e - l .T .) (1-1 / l .T)]. D / L .T and realize
that the D / T is the dose rate R . In
the general Lea-Catchesid integral, the dose rate R
appears directly.
2. Repopulation
In addition to the exponential decrease in the number of cells
due to radiation damage, there is a continuous replacement of
extinct cells by dividing the surviving cells. Over the time
interval D t, the number N of existing cells increases by N. n . D t, where n is the rate
of cell repopulation ; the doubling
time T 2r = ln2 / n of the number of cells by repopulation is often used .
Integration yields an exponential law of cell number growth by
repopulating N = N 0 .e n .T . In logarithmic
form, this leads to another additive term RP = ln2.T / T 2r ,
expressing the ratio of irradiation time T and time T2r
doubling of cell number by repopulation. Cell repopulation
further enhances the above dose rate effect .
Including these time effects, the linear-quadratic
dependence takes the final form (on a semi-logarithmic scale):
-ln (N / N 0 ) = a .D + { 2. [(1-e - l .T ). (1-1 / l .T)] / l .T } . b .D 2 - ln2.T / T 2r .
These relationships between the biological effect and
the radiation dose, including its time course (irradiation time
T), play an important role, especially in radiotherapy,
where fractionation of irradiation doses is used in
order to optimize the resulting radiation response of tumor
tissue with respect to healthy tissue - see §3.6 " Radiotherapy
". An interesting consequence of the above dependences of
the LQ model may be the absence of a deterministic effect
even at relatively high total radiation doses (significantly
higher than the thresholds for single irradiation according to
Fig. 5.2.3b), if irradiation is long-term with dose rate lower
than cell repair and repopulation. In this case, only stochastic
effects can occur.
Deviations from the LQ model. Alternative
models and dependencies.
The linear-quadratic model is only a simplified mechanistic
description of complex processes taking place during
ionizing irradiation of tissues and cell populations. In
practice, there are some deviations from the
standard (idealized) LQ model .
Higher powers of the
dose
A double DNA break is usually
considered unrecoverable, leading to inactivation and mitotic
cell death. However, later experiments have shown that even such
damage can sometimes be repaired by the cell, albeit with less
probability. In addition to the first and second powers, it is
sometimes necessary to include smaller corrections containing higher
powers of the dose in the dose dependence of the
radiobiological effect (Fig. 5.2.4a). They could partly have
their origins in multiple interactions (simultaneous or
rapidly consecutive) of quantum ionizing radiation, resp. their
fumes, with cell nuclei that are more difficult to repair repair
mechanisms. In reality, however, many different influences apply
here. This is especially evident in densely ionizing
radiation (with a high value of linear LET energy transfer),
where, in addition, the transmitted energy is distributed unevenly
(especially in the region of the Bragg maximum for radiation a , protons and
other heavy charged particles). Dependence [ln (N / N 0 )] (D) can then
develop into a Taylor series by the various squares of
the dose D .
Tissue
biological influences.
Even more significant are some individual biological
influences . Each tissue is in fact a heterogeneous
cell population , containing cells at different stages of
the cell cycle and cells with different radiosensitivity
- with different coefficients a,
b : the resulting survival curve [ln (N / N
0 )] (D)
is then a superposition of several different LQs. curves. In
addition, during self-exposure, cell redistribution
may occur (change in the relative proportion of cells with
different radiosensitivity: a decrease in the proportion of G1
and G2 cells and total clonogenic cells, while M and S cells and
effector daughter cells will have a relatively higher
proportion). ) during irradiation or reoxygenation
(change in oxygen content - the above-mentioned "oxygen
effect"). The oxygen effect is significant especially when
using sparsely ionizing radiation (photon radiation g or X is most often
used ), where the indirect radical mechanism of the radiation
effect predominates. In densely ionizing radiation, where there
is an increased proportion of the direct intervention mechanism
(and also increased radical recombination), the effect of oxygen
(oxygenation) on the radiobiological effects is less significant.
These biological processes can result in changes in the
radiation sensitivity of cells and tissues during
exposure, leading to further deviations from the LQ model
dependencies. Bystander
effect
The so-called bystander effect of
remote induction of radiation effects in tissue is also discussed
(described above in the section "Effects of radiation at the tissue level "), which may slightly increase the number
of damaged cells (Fig. 5.2.4b). The effect of the
bystander effect can be included in the LQ model by inserting a
new empirical coefficient B> 1, indicating the average number
of damaged cells when one cell is hit: N / N 0 = e - b
( a .D + b
.D 2
) . But this is equivalent to a
standard LQ model with slightly higher values for the parameters a ' = B.a , b ' = B. b . the resulting
coefficients radiosensitivity a
' , b ´ for the tissue are therefore slightly higher than the
coefficients due to the bystander effect a , b for individual cells.
Factor B is different for different tissues. In practical
radiobiological experiments, however, radiosensitivity is
determined for tissue (or tissue cultures), where the effect of
the bystander effect is already implicitly contained: a®a ´, b®b ´. The LQ
model for practical use therefore remains unchanged
. The bystander effect does not change the basic principles and
dependencies of the LQ model, it only causes differences in
radiosensitivity between the cell and tissue levels.
Fig.5.2.4. Some deviations from the LQ model of dose-response of
biological effect.
a) Multiple radiation interaction with the cells
resulted in the presence of members of the higher power of the
dose D . b) The bystander effect slightly
increases the total number of damaged cells (decreases the
fraction of surviving cells). c) In the area of
??low doses, a relatively increased cell sensitivity -
hyperradiosensitivity - is observed on the graph of the surviving
fraction of cells.
Hyper-radiosensitivity
to low doses. Induced repair model
The higher the absorbed dose of ionizing radiation, the greater
the amount of free radicals generated - the greater the damage to
cells in the tissue or cell population. And the higher the
percentage of cells killed: the dose dependence of the N / N 0 of the surviving
fraction of cells should be monotonically decreasing .
However, some radiobiological experiments have shown that in the
area of ??very low doses (approx. 0.1-0.5 Gy) the otherwise
gradually decreasing, almost linear dependence of N / N 0 of the surviving
fraction of cells (according to Fig. 5.2.3c) has a significant
"valley" , showing a relatively increased
sensitivity of cells than would correspond to these low
doses (Fig. 5.2.4c) - so-called hyper-radiosensitivity
to low doses for deterministic effects. The cells start to
repair only after a certain dose ...
The detailed mechanism of this
paradoxical behavior is not yet known. It may be related to the
kinetics of enzymes in the G2 phase of the cell cycle during
reparations by homologous recombination (see
the "Nitrocellular Repairs " section above) , where the
concentration of enzymes increases with increasing dose, inducing
an increased rate of reparations. Thus, at the cellular level, it
appears that cells may need some low level of damage to initiate
the production of repair enzymes by feedback processes. If at low
doses this level is reached, the reparations did not work and the
check-point would be next mitosis stopped ® inactivation of cell ® higher
sensitivity to low doses. At a higher dose (and thus greater DNA
damage), the production of repair enzymes would already take
place ® more efficient repair ® relatively lower
sensitivity - the dependence returns to the standard curve of the
LQ model. This phenomenon is sometimes referred to as induced
repair .
Note
1: A
"physiological defense mechanism" against the mutagenic
effects of radiation in the area of ??increased probability of
survival of cells with partially impaired genetic information is
also being considered vaguely; these cells die due to
hypersensitivity (in the spirit of the above-mentioned motto for
damaged cells " dead cell = good cell ") and
do not endanger the organism with later stochastic effects.
Note 2:The
mechanism of radiation-induced repair could contribute to radiation
hormesis discussed below in the section " Low doses of radiation: - are they harmful
or beneficial? ".
Note 3:
A kind of "prototype" low dose hyperradiosenzitivity
perhaps could be called. Petkau effect
( Petkóùv phenomenon ), who in 1972 described the
Canadian Radiobiology A.Petkau. It was allegedly an increased
destruction of cell membranes during long-term irradiation with
very low doses of radiation. He explained the mechanism of action
of negative oxygen ions, which at lower concentrations damage the
membranes more, while at higher concentrations they have greater
recombination and less effect. This explanation is not very
convincing and the Patkau phenomenon itselfwas not
confirmed by later radiobiological studies (it was
observed at a time when technical means or radiobiological
knowledge did not yet allow to reliably demonstrate such a
phenomenon or reveal its mechanism; it could be a chemical effect
of carriers of used radionuclide 22 Na, or similar side effects. ). In light of current
radiobiological findings, the primary effect of a low dose should
be on DNA whose uncorrected damage induces cell apoptosis with
secondary cell membrane damage (as discussed in the " Mechanisms
of Cell Death " section above).
Not much was known about cell apoptosis at that time.
Within the LQ model with standard
parameters a, b hyperradiosensitivity can be included by inserting an
initial component with a higher parameter value a hyper > a - assuming a dose dependence of the parameter a : a (D) = a + ( a hyper - a ) .e - D / D hyper , where a hyper is the initial
higher value describing slope [ln (N / N 0 )] (D) for low doses, a the default value for the
higher dose D hyper ( » 0.2 g) is a boundary area hyperradiosenzitivity
expression. LQ model N / N 0= e - [ a (D) .D + b
.D 2
] with such a dose-dependent
parameter a (D) then captures the experimental data well. For high
doses D >> D hyper turns into a standard LQ model with the usual
parameters a, b , for low doses D << D hyper behaves as an LQ model with parameters ahyper , b . It is thus a combination
of two LQ models with different a -ensitivities (two
different directives in Fig. 5.2.4c), combined into one equation;
it is sometimes called the IndRep model (induced
repair).
Notice: Please do not confuse this
physiological (relative) low-dose
hyper-radiosensitivity, inherent in all cells, with pathologically
increased overall radiosensitivity due to genetic disorders of chromosomal
instability - mentioned above in the section " Dose-biological
relationship ".
(multi) Target model
This simple and largely phenomenological model is the predecessor
of the LQ model. It is based on the assumption that there are one
or more radiation- sensitive targets in the cell
. If one of these targets is hit (by radiation or radical), it
leads to cell inactivation and death. If one is present
such a target, then by an analogous application of Poison's
statistical distribution of the probabilities of intervention,
which we used above for the a -
process in the LQ model, we get the
dependence of the surviving fraction of cells N / N 0 on the dose D
: N / N 0
= e - D / D o , where D o is the dose that leads on average to one hit of the
target. If n targets are present , then the multi-target
model of single-intervention inactivation gives the
dependence: N / N 0 = 1 - (1 - e -
D / D o ) n. To obtain better
agreement with experimental values in the low dose range,
sometimes the n-target dependence is combined with the 1-target
dependence (each with a different value of the empirical constant
D o ).
Kinetic models of DNA
breaks - LPL and RMR model
Models based on the analysis of the kinetics of such DNA breaks
come from the 1980s, which may (but may not) result in the
killing of cells. Models lethal and potentially lethal effect
(LPL SBCurtis 1989), and corrected / neopraveného damage
(repair / misrepair model - RMR, CATobias 1985), sometimes unite
into so-called. Model of two lesions TLK (two-lesion
kinetic) are for the usual doses (units up to tens of Gy)
practically identical to the LQ model.
The local effect model
Local Effect Model (LEM ) takes into account the local dose
distribution along the path of ionizing radiation, in relation to
the dimensions and density of the distribution of cell nuclei in
the irradiated tissue. It is based on a simple general
relationship N / N 0 = e - N (D) , where N (D) is the average number of
lethal lesions per cell at dose D (only the a -process is taken
into account). It then introduces the local volume density of
lethal lesions with (D) = N (D) / V, (where V
is the average volume of cell nuclei),
which relates to the local density of the dose distribution along
the path of the particles for different types of radiation.
Through this analysis model better describes the biological
effects of densely ionizing radiation (proton, a particles capable
of, radiation, heavy ions).
Two-stage stochastic
model
This further improvement in the modeling of the radiobiological
effect was developed by our experts (P. Kundrát, M. Lokajíèek,
H. Hromèíková). As in the classical LQ model, it is based on
the analysis of cell damage by lethal a - process
and less severe damage by b-
process , which is in
principle repairable, but a combination of two b-damage is lethal.
Using Poisson statistics, the probability of the cell (cell
nucleus) hitting a certain number of particles depending on the
dose, LET and size of the nucleus is analyzed, as well as the
probability of cell survival after repair processes. In this
analysis, it is assumed that the condition for the survival of
the cell after a given number of interventions by the ionizing
particle is no damage by the a - process and a maximum of
one damage by the b- process, as well as its successful repair. The model is
elaborated especially for proton and ion radiation.
High-dose modifications
of the LQ model - LQL, gLQ, USC, KN, PLQ
When irradiated with high doses of radiation
(d> 5.10 or more Gy / fraction), which allow
advanced conformal techniques of stereotactic radiotherapy and
HDR brachytherapy (§3.5, section " Stereotactic
radiotherapy SBRT "), showed
some discrepancy between expected and observed effects:
the classical LQ model in these at higher doses per fraction
somewhat overestimates the biological effect of radiotherapy,
predicting higher damage to normal tissue NTCP. As if the curves
of the surviving fraction of cells -ln (N / N o ) (on a log-linear
scale) at higher doses actually showed an increased proportion of
the linear component than the quadratic. To capture this clinical
knowledge, some empirical modifications of the LQ model
are sometimes used that better capture the radiobiological
effects inat higher doses :
× LQL
model ( linear-quadratic-linear ) for higher
doses / fraction (higher than 2. a / b , in practice>
approx. 6Gy) adds an additional linear component
increasing the surviving fraction of cells.
× Generalized gLQ model (
generalized LQ ). The standard (conventional) LQ model
assumes that the velocity l repair of radiation-induced sublethal damage
remains constant over time, leading to an exponential repair
pattern in the Lea-Cathesid term RG. However, some experimental
studies suggest that the repair rate of sublethal lesions slows
over time. The generalization in the gLQ model consists in
introducing a reparation term with a reciprocal time of 1 / T
into the Lea-Cathesid term RG.
× Universal
Survival Curve ( USC ), which is compiled
for the high dose area based on a combination of the LQ
model (which gives a good description for small and medium
doses) and the multi-target MT model (better describing
the effect at higher doses - dependence in this area it is based
more as a straight line).
× The KN ( Kavahagh-Newman
) model introduces another dose-dependent factor
into the b- member in the LQ model: ln (N / N 0 ) = - a .D - b .D 2. [1 + ( b / g ) .D] - 1 .
× PLQ
( Pade Linear Quadratic ) model
introduces an additional dose-dependent factor into the overall
expression for the probability of cell survival in the LQ model:
ln (N / N 0
) = (- a .D - b .D 2 ). (1 + g .D ) -1
(The name comes from the fact that the expression can be modeled
as a Padé-approximation of the ratio of two
polynomials) .
Phenomenological
character of the LQ model ?
All the above-mentioned complex
processes at the level of cells, cell populations and tissues
(whose mechanisms are often not yet examined in detail) cause in
practice the coefficients a,
b in the LQ model sometimes lose their
unambiguous physical or radiobiological significance and take on
the character of empirical constants . In the area of
??radiation doses used in biological applications (units up to
tens of Gy), they model the real dependence of the N / N
0 of the
surviving fraction of cells on the dose, but the LQ model itself
becomes rather summary phenomenological description of the
biological effect of radiation. Nevertheless, this model, based
on a precise analysis of the relevant mechanisms, remains the
best and most sophisticated model of dose dependence of
the radiobiological effect for practical use.
Small doses of radiation: - are
they harmful or beneficial?
or
Will the basic
paradigm of radiation protection change?
"Any irradiation of healthy living
tissue with ionizing radiation, even at a very small dose, can be
potentially dangerous to the body due to its late stochastic
effects. Therefore, it is necessary to reduce radiation doses to
a minimum by all available means."
In the extreme case, even a single quantity of ionizing radiation
that enters the body can damage the DNA in the cell and
eventually lead to cancer ..?! ..
This is the basic premise of
the current radiation protection, "canonized" in all
standards and regulations for working with ionizing radiation,
including our "Atomic Law". In this section, we will
try to question this basic paradigm of radiation
protection a bit "heretically" - we will discuss some alternative
views on the risks of low-dose exposure.
On what factual data is
this basic basis of radiation protection based? In addition to
experiments on small animals (rats), criminal abuses of nuclear
forces in Hiroshima and Nagasaki, as well as a number of
radiation accidents, have become a source of data on the
biological effects of radiation. During these tragic events, many
people were irradiated with various doses of radiation, including
very high and lethal doses. Radiobiology and radiation medicine
thus gained a fairly good idea of ??the deterministic
effects of radiation, the course of radiation sickness
and the possibilities of its treatment. Long-term follow-up of a
number of people who received lower doses than corresponded to
acute radiation sickness also provided important information
about stochastic effects of radiation and their
dose-dependence. Further data on deterministic and stochastic
effects of radiation were obtained by monitoring large groups of
patients irradiated in medical therapeutic and diagnostic
applications ( radiotoxicity, secondary post-radiation
malignancies ).
"Linear
threshold-free theory" is only an unsubstantiated hypothesis
A common feature of most studies on the biological effects of
ionizing radiation is that these are medium , higher,
and high doses (from a few tenths of Sv to many
tens of Sv). For these values ??it is possible to construct a
fairly objective relationship between the dose value and
biological effects (Fig. 5.2.3). As for the lowest doses
(at the level of units and tens of mSv), it must be admitted that
it is a "terra incognita" where reliable data
are lacking *); It is not surprising, because the label
"stochastic effects" itself says that it is difficult
to find any causal patterns here ...
*) For medium and higher doses (in the area
above about 400mGy) the relationship between dose and effect is proven
and statistically significant. However, towards lower doses, the
results are blurred due to statistical fluctuations and
uncertainties; for the lowest doses, the biological effect is
no longer statistically detectable. Given the assumed
roughly linear dose-effect relationship, the number of
individuals required to demonstrate the statistical significance
of a stochastic effect increases with the inverted square of the
average dose required to produce the effect. If the effect at
doses around 1 Gy is demonstrable in a statistical group of
several thousand people, then the demonstration of the effect
conditioned by a dose of 0.1 Gy requires a hundred thousand
group. For the lowest doses close to zero, the existence of a natural
radiation background completely makes it
impossible to analyze the relationship between dose and
radiation effect. Furthermore, a number of disturbing side "masking"
factors can manifest themselves here , completely
distorting the observed results!
Conservative
radiobiologists and radiation protection experts will therefore
take the point [0,0] as a starting point (zero dose = zero
effect), interpolate the linear dependence from zero to the
actually proven values ??and replace the missing values
in the lowest dose range with extrapolated hypothetical
values (straight line on Fig.5.2.3 left). And right here
we have a claim about the harmful stochastic effects and the
lowest doses of radiation, or the thresholdlessness of
stochastic effects. Claims often repeated (and therefore
generally accepted), but unproven ! Linear
threshold-free theory is not a radiobiological hypothesis, but is
the result of processing and straightforward approximation of
available data.
Careful analysis of the
data collected on dose-response relationships shows that the
dose-response is unlikely to be linear
. The effects in the area of ??low doses are probably smaller
than would correspond to the previously assumed linear dependence
(a blue or green curve in Fig. 5.2.3 on the left is possible
closer to reality). The assumption of linear dependence and
thresholdlessness of stochastic effects, on which the current
concept of radiation protection is built, represents a conservative
approach , overestimating the risks in the area of
??small doses.
Let's turn to the
argument from another direction - the development of lifeon
Earth and the role of repair processes in cell nuclei. The basic
mechanism of genetic transmission of information in primitive
cells evolved hundreds of millions of years ago, when the level
of natural ionizing radiation was much
higher than today (higher natural radioactivity, lower
shielding ability of the atmosphere against cosmic radiation).
This high level of radiation background was both an important driving
force in the evolution of life (mutations + natural
selection ® development of new species) and forced cells to develop
sufficiently effective repair mechanisms against
radiation damage. And they probably retained
these mechanismsits effectiveness to this day. Even now, due to
natural radioactivity and cosmic radiation, our organism is
irradiated with several thousand quanta of ionizing radiation
every second.
A large amount of
reactive radicals and oxidants are formed as products of normal metabolism
in the body; there are even many more than when irradiated with
low or medium doses of ionizing radiation (it is estimated at
hundreds of thousands of DNA nucleotide damage in each cell per
day). It can therefore be expected that harmful radicals caused
by a small dose of ionizing radiation will be lost
"like a drop in the sea" of a large amount of harmful
products of normal metabolism.
Note:This roughly
applies to "sparsely" ionizing radiation.
"Densely" ionizing radiation causes double DNA breaks
that are less repairable, leading to higher radiobiological
efficacy, including a higher risk of stochastic effects.
Radiation
hormesis and adaptive response
In addition, some experts believe that a reasonable number of
disorders caused by a small dose of radiation (especially sparse
ionizing radiation) can initiate and stimulate
chromosome-level repair mechanisms in the body
that "not only" correct these radiation disorders, but
also "take in" a number of other metabolic defects that
might otherwise remain uncorrected. This radiation
hormesis *), or adaptive response or radiation-induced
repair at low irradiation of cells and organisms, there
is a kind of "immunization" in the organism.
*) Hormesis
The word hormesis comes from Greek. " hormaein
" = " excite, excite, strengthenThis is an
experience-based phenomenon in which low doses of toxic
substances not only do not damage the organism, but even improve
its physiological functions. - factors that disrupt the
functioning of the organism, which are often responded to by
adaptation (adaptation), the action of small amounts of toxic
substances that damage biological molecules, triggers a stress
response and can lead to hormesis, and the body tolerates higher
doses of the toxic substance. of these factors stimulating
hormesis, ionizing radiation could also be ...
According to
these opinions (but also not yet reliably proven), small doses of
radiation could even be beneficial for the
organism! A low dose of radiation triggers the "signal"
emitted by the damaged DNA, and the subsequent repair process
corrects any errors found (and removes those nucleotides that
cannot be repaired), not just those caused by the radiation. If
the amount of damage caused by the radiation is less than the
"capacity" of the repair system, other errors shall be
corrected; after irradiation with a small dose, there are fewer
errors in the DNA than before - there is a positive
effect (the section of the green curve below the horizontal axis
in Fig. 5.2.3a). At a higher dose, when the extent of radiation
damage exceeds the "repair capacity", the effect of
irradiation is already negative (the rest of the
green curve in positive values).
Several mechanisms can be used in the radiation adaptive response
:
¨ Time
- slowing down the cell cycle, so that by
the beginning of the next mitosis, some damage can be repaired;
¨ Chemical - neutralization and thus
detoxification of reactive radicals;
¨ Biochemical -
activation of enzymes involved in intracellular repair - the
above-mentioned radiation-induced repair
;
¨ Immune - stimulation of
defense mechanisms at the level of the whole organism, which
could help eliminate cells changed not only by radiation.
A certain small "preparatory" or
"preventive" dose of radiation can thus protect
the cells against damage caused by a subsequent much
higher dose. A small dose activates in the cell, enzymes designed to correct genetic
information, making it easier for the cell to deal with the
possible consequences of stronger radiation. Regarding the effect
of radiation on complex multicellular organisms, there is also
the opinion that a small dose of radiation or some toxins
deprives the organism of cells that have weakened repair
mechanisms and which would be in danger of succumbing to
malignancy in the future.
These (so far)
non-conforming opinions were also verified experimentally
. Of course, it would be ethically unacceptable to perform such
experiments on humans, and not even on higher animals. However,
interesting experiments were performed on bacteria . The bacterial culture (.......) was divided into two
parts, one of which was placed in a well-shielded box, where the
level of radiation background was lower than in nature. The
second group of bacteria was exposed to a weak field of ionizing
radiation under the same other conditions (temperature, pressure,
humidity, nutrients). A surprising result was found: bacteria
exposed to radiation prospered somewhat better than bacteria from
the second group shielded from radiation! However, it was a
question of monitoring the entire culture of bacteria (the
reproduction of which could show selective effects), not of
monitoring individual effects on individual bacteria.
It is clear
that there is no straightforward transfer of these experimental
results and speculative considerations to the biological effects
of radiation on humans. Bacteria are prokaryotic organisms which,
due to their unicellularity, cannot, of course, develop cancer.
We are eukaryotes with a large number of cells of different
species, interconnected by a number of complex signaling
pathways; it is this circumstance that enables the development of
cancer due to cytogenetic mutations, including the action of
ionizing radiation. However, much here may depend on the function
and extent of radiation-induced repair.
Only further research in
the field of molecular biochemistry and cytology, as well as more
extensive epidemiological studies, will hopefully help to clarify
the question of the effect of small doses of radiation. Until
this is reliably clarified, it is in viewreliability of
radiation protection, it is necessary to apply in
practice a linear threshold-free theory, which in the area of
??small doses is associated with a slight overestimation of risk
and a low probability of possible underestimation.
However, if
the above conclusions are demonstrated in further experiments and
subsequently in clinical studies, a change in the
conservative paradigm of current radiation protection in
the field of low radiation doses can be expected in the future
and subsequently a revision of relevant
standards and regulations. However , radiophobia
, which is deeply rooted in Western society due to the mass
media, will probably persist for a very long time ...
Time
course and types of biological effects of radiation
In terms of the time of onset and time course of the effects of
radiation on the organism, or its tissues and organs, we
distinguish two groups :
× Early effects of
irradiation
develop within a relatively short time (days to weeks) after a
single irradiation with a larger dose of radiation. They are
caused by the extinction of a significant part of the cells of
irradiated tissue, especially stem cells, in rapidly
proliferating tissues, in which there is a need for continuous
rapid renewal of daughter effector cells that have a short life
cycle. Stem cell depletion soon results in a
loss of effector cells, which is reflected in deterioration of
irradiated tissue function. These tissues (eg hematopoietic
tissue or mucosal cells) have a high radiosensitivity and a rapid
response to irradiation. These are acute deterministic effects
and the rule is that the higher the dose, the earlier
the effects start and the more severe
they are. If too many stem cells are not damaged, after
overcoming these early effects, there is also a relatively rapid
recovery of the tissue by cell repopulation
(accelerated stem cell division, or a
temporary loss of division asymmetry in favor of effector cells) and its return to normal function. However, late
radiation effects (deterministic and stochastic), discussed
below , may occur over a longer period of time .
Very early radiotoxic
effects
When exposed to a high dose of radiation all over the body, very
early, within a few hours, very early symptoms of a stress
reaction of the organism, such as fatigue, nausea, dry mouth, may
appear. These manifestations of very early radiotoxicity
they are not caused by the mechanisms of radiation killing of
cells - a larger number of cells are damaged, but this damage
will appear later, only during the mitosis of these cells. Very
early radiotoxicity is caused by irritation of the
body's regulatory centers (nervous and humoral) by
direct exposure to released ions, radicals and other
products of radiolysis . At very high doses
(hundreds of Gy once), very rapid and fatal radiotoxic effects
can occur due to denaturation of the cell contents
(rapid necrotic cell death) and the intercellular environment.
The
early effects of radiation - early radiotoxicity
- include :
× Late effects of
irradiation
can manifest themselves after several months, years to decades of
latency from irradiation. They arise either as deterministic
effects after intense irradiation, long-term or repeated
exposure to smaller doses of radiation (non-tumor late damage - late
radiotoxicity ), or as stochastic effects
(cancer and genetic disorders). Late deterministic effects are
caused by tissue damage with slow effector cell regeneration and
thus low stem cell proliferative activity. Damage to stem cells
by irradiation will only become apparent when their mitosis is
needed to replenish effector cells, which is usually several
months apart. Only then do damaged stem cells die and the tissue
begins to show a lack of effector cells. Tissues of this type
(such as connective tissue, muscle tissue, kidney) with slow cell
division have low radiosensitivity and slow response to
irradiation. However, the effects persist for a long time,
sometimes even permanently.
Combination of early
and late radiation effects
Individual organs are often made up of different types of
functionally connected tissues - reacting quickly and late,
within one organ. Therefore, early acute radiotoxicity occurs
during irradiation, after its disappearance, subsequent
(consequential) late radiotoxicity may manifest over time. E.g.
during irradiation of the lungs, late lung fibrosis may gradually
develop after acute radiation pneumonitis.
The late types of radiation include the
following types of radiation damage (the
first two are deterministic, the second two are stochastic) :
Local tissue and organ radiation
effects
We first analyzed the biological radiation effects at the molecular-cellular
and tissue level in general (see above
" Effects of radiation on cells ",
" Radiation effects during the cell cycle
") . We have shown different
sensitivity of cells in individual phases of the cell cycle and
the resulting difference in radiosensitivity for stem and
effector cells, as well as for different tissues and organs. We
further analyzed the dependence of biological effects on the size
of the absorbed dose and its time course ("
Linear-quadratic model of deterministic radiation effect
") . Then we focused on the radiation
effects on the organism, especially in whole body
irradiation .
However, a frequent case of radiation exposure
is the dominant exposure of only a certain part of the
body, a certain organ or tissue. Especially in the case of radiotherapeutic
use of ionizing radiation (§3.6 " Radiotherapy
") , a carefully selected part is
exposed - the tumor lesion (target volume), while the surrounding
healthy tissues and organs also receive certain doses. In these
cases, specific aspects of radiation sensitivity and the response
of different tissue and organ types to different spatio-temporal
dose distributions are very important . From the
point of view of the nature of sensitivity to the spatial
distribution of the radiation dose in tissues and
organs, it is important "Organizational structure
"and the size of individual functional parts. In general,
organisms are composed of cells, grouping into tissues and
functional units - organs . Organs
consist of smaller groups of cells that provide function in
individual parts of the organ - the so-called functional
subunits . Functional subunits have different
sizes and are differently interconnected and organized within a
given body, event. its links to other tissues and organs. According to the arrangement of functional subunits,
biological organs can be divided into two basic types :
¨ A
serial organ
is made up of a number of linearly arranged cellular structures
(functional subunits), which are functionally arranged in
series (in series). The specialized activity of
the cells of one section functionally follows the activity of the
cells of the previous section. Local damage to even a relatively
small place (section) can lead to a "failure" of the
function of the entire adjoining organ. Examples of serial organs
are spinal cord, optic nerve, esophagus, ureter, intestine and
the like.
¨ A
parallel organ
consists of many cellular structures (functional subunits) of
roughly the same function, which occupy a larger space
and are arranged side by side (in parallel
), working "together". Local damage to a smaller volume
of such tissue is not significantly reflected in the activity of
the whole organ, the remaining cells are enough to functionally
cover its activity for the organism - these organs have a
significant functional reserve. Examples of
parallel organs are the liver, lungs, kidneys, thyroid gland,
spleen, etc.
In a detailed view, the series and
parallel arrangement is partially combined - for
example, the parts connected in parallel with the local series
arrangement of the elementary functional subunits. And organ
systems or tracts (GIT, urinary tract) are a complex
series-parallel arrangement of many different parts and
functional subunits.
Serial and parallel organs have different
radiobiological behavior in terms of spatial
distribution of radiation dose. Serial organs may relatively well
tolerate a dose evenly distributed over its entire volume, or
whole body dose, but are very sensitive to high local
dose which can "disable" them. Parallel organs
behave in the opposite way, which tolerate even a very high local
dose to a small volume (the elimination of which will reduce the
function only insignificantly), but they are damaged by
the total dose to their entire volume, resp. depends on
the total volume of irradiated tissue. This different nature of
the radiation sensitivity of serial and parallel organs to the
spatial distribution of the dose is of great importance in radiotherapy
, where serial organs in particular often act as so-called critical
organs , for which the tolerance dose
should not be exceeded (see §3.6 " Radiotherapy
").
Sources
of radiation from ionizing radiation
Throughout the duration and evolution of life on Earth, all
organisms are exposed to ionizing radiation from natural
sources - cosmic radiation (§1.5.,
Part " Cosmic radiation ") and natural radionuclides
(§1.4., Part " Natural
radionuclides " ) . The same is true throughout the existence of man.
Since the beginning of the 20th century, after the discovery of
X-rays and radioactivity, a number of artificial sources
of ionizing radiation have been approaching natural
sources , which are increasingly used in many fields of medicine,
research and industry. Depending on their physical and chemical
properties, sources of ionizing radiation cause either external
orinternal irradiation . External radiation is
caused by sources located outside the body, internal radiation is
caused by radiation from radionuclides found in the human body.
The method of irradiation and specific doses of radiation further
depend on the occurrence and movement of individual sources
(natural and artificial) in the environment.
N
a t u r a l --- A r t i f i c. |
Radiation source | Effective
dose [mSv / year] |
Share [%] |
88% ----- 12% |
Radon (and its decay products) | 2.1 | 48 | ||
Terrestrial (terrestrial) radiation | 0.45 | 17 | ||
Internal irradiation with natural radionuclides in the body | 0.25 | 9 | ||
Cosmic radiation (secondary) | 0.4 | 14 | ||
-------------------------------------------- | ------------- | ---- | ||
Medical irradiation (diagnostics, therapy) | 0.3 | 11 | ||
Occupational exposure | 0.002 | 0.08 | ||
Technical and consumer items | 0.005 | 0.02 | ||
Nuclear energy (excluding accidents) | 0.001 | 0.04 | ||
Radioactive fallout (nuclear weapons and accidents) | 0.005 | 0.02 |
Approximate values of the average radiation dose from individual radiation sources per 1 person per 1 year |
The average annual dose from irradiation from natural sources for humans is about 3.2 mSv, from artificial sources it is estimated at about 0.3 mSv / year. At present, therefore, on average, about 90% of the radiation exposure is from natural sources and 10% from artificial sources; in any case, these are, on average, very small doses of radiation .
Natural
sources of ionizing radiation
In our environment, we are constantly exposed to ionizing
radiation from cosmic radiation and from natural
radionuclides in the air, in surrounding objects, in soil and
rocks, building materials and in our bodies. Natural sources
causing radiation dose in living organisms and humans can be
divided into three components according to their nature and
significance :
Artificial
sources of ionizing radiation
Ionizing radiation from artificial sources can be divided into
three categories according to its nature and radiation
significance :
5.3. Objectives and methods of radiation protection
Basic goals of
radiation protection
Proven harmful deterministic effects of strong
radiation *), as well as the risk of harmful
stochastic effects of weak radiation (apart from the
above-mentioned alternative possibilities of low radiation
doses), leads to the need for protection against ionizing
radiation . This radiation protection
or radiation hygiene represents a system of
technical and organizational measures to reduce unwanted exposure
of physical organisms (especially persons) and to protect the
environment from this radiation.
*) By this we mean, of course, the harmful effects of radiation
on healthy tissue , not the targeted
deterministic effects on pathological foci in
radiotherapy that are beneficial for the
organism (see chapter 3.6 " Radiotherapy
")!
The basic goal
of radiation protection can therefore be formulated as
follows :
The aim of radiation protection is to eliminate the deterministic effects of ionizing radiation and to reduce the probability of stochastic effects to a reasonably achievable level. |
The risk from ionizing radiation is in addition
to the other risks we are exposed to during our lives -
environmental and food pollutants, smoking, genetic influences,
infectious and other diseases, etc.
From a statistical
point of view, these risks are sometimes compared
against certain nominal risk factors . These
nominal risk factors are determined statistically
from a certain additional frequency of illness or death depending
on the risk factors. However, the accuracy of such determinations
is uncertain and debatable, there are a number
of factors and selection effects , often unknown.
Therefore, in our physically focused treatise on the effects of
radiation and radiation protection, we do not address these
issues.
The
specific nature of ionizing radiation of the organism
Compared to most other pollutants that affect our organisms,
ionizing radiation has its distinctive specifics :
¨ Ionizing
radiation is not affected by our senses .
If a person is in a place exposed to ionizing radiation, he does
not feel it . And even at high intensities *),
when the radiation dose soon exceeds the lethal value! If we do
not have a suitable radiometer "on hand", we cannot
assess the danger of this situation.
*) At high radiation intensities, ozone,
which can be smelled in the air, can be a warning signal.
¨ Initial symptoms of radiation
sickness
is virtually indistinguishable from the initial symptoms of
common diseases such as the common cold or flu. If radiation is
not suspected, radiation sickness may not be detected in time and
treated adequately.
¨ Prolonged
clinical manifestation of late effects of radiation
at doses up to about 3Gy, and especially stochastic effects, may
lead to the fact that we will not associate any health problems
with radiation in the past.
¨ Low level of knowledge
in the fields of nuclear physics, radioactivity and ionizing
radiation in the general human population. This leads to an
underestimation or overestimation of the risks of radiation and
radiation protection, the emergence of various misinformations
and rumors (such as radiophobia and resistance to nuclear
energy).
Principles
of radiation protection
In general, three basic principles are used to ensure the
objectives of radiation hygiene :
These general principles of radiation protection have their specific form in medical applications of ionizing radiation, see §5.7 " Radiation protection in radiation diagnosis and therapy ". Part of radiation protection is also ensuring the physical safety of sources of ionizing radiation, which should be secured so that there can be no uncontrolled irradiation or contamination of the environment - so that the sources are properly stored and recorded, so that the source is not lost or stolen, so that emitters are entrusted. only to persons and organizations who are trained and authorized for the relevant activities.
Basic
methods of radiation protection
The task of radiation protection is to reduce the
absorbed dose of ionizing radiation in the organism to
the lowest possible level (reasonably
achievable - "ALARA") and thus
significantly reduce the risk of adverse
deterministic or stochastic effects of radiation. The radiation dose received is
determined by several basic factors: the intensity
, type and energy of
the emitted radiation we work with, the exposure time and the
geometric conditions (distance, shielding). So
there are three basic
ways to protect against external ionizing radiation (+ the fourth
way when working with open emitters) :
Unjustified radiophobia when working with radiation: |
With erudite work with knowledge of the matter and adherence to the principles of radiation protection, it can be achieved that working with ionizing radiation is no more dangerous and harmful than working with any other materials, machines and equipment. |
The practical implementation of the above principles of radiation protection can be significantly aided by the use of protective aids in individual work operations with ionizing radiation. On the one hand, they are shielding aids - lead cases, covers, containers or containers for radiators, shielding walls, aprons, glasses, etc. Furthermore, handling aids - tweezers, pipettes, remote manipulators, conveyors, etc. When working with open emitters, they are aids against contamination - rubber gloves, coats, veils, airtight shoes and more.
Radiation dose limits
Any dose of ionizing radiation can be associated with a certain
risk of harmful effects (at least according
to the linear threshold-free hypothesis ...) , so care must be taken to keep
the doses as low as possible. For the purposes of assessing and
controlling radiation exposure, certain dose limits *) have been
set per year and for 5 years - the so-called limits (maximum permissible doses) for workers
with ionizing radiation sources, which are still associated with
a very low probability of radiation damage. The current value of
the annual limit for workers was set at 50
mSv , the five-year
limit at 100 mSv (5 consecutive years) . Basic limits for other
populations are set at 1 mSv / year .
*) These are additional
benefits to benefits from natural sources. Spontaneous radiation
dose from natural sources with the limits for residents or for
occupational exposure to radiation workers counted
(counted However, in cases of targeted and
professional activities associated with increased exposure from
natural sources - such as working in uranium mines or in high
aircraft) .
...........
5.4.
Radiation monitoring and personal dosimetry
Radiation monitoring is a targeted measurement
of quantities characterizing radiation in order to
ensure the optimal level of protection of persons and the work or
environment from the harmful effects of ionizing radiation.
Monitoring is performed at workplaces with ionizing radiation and
possibly even in the vicinity of major sources of ionizing
radiation. The basic quantities measured during radiation
monitoring are the radiation dose and dose rate.
Their direct measurement is performed using so-called dosimeters
, which are specially modified radiometers, calibrated in dose
units (Gray, Sievert). In addition, derived dose
determination methods are used based on other quantities, eg
radionuclide activity.
Reference levels
For the evaluation of measurement results during monitoring,
learned significant values are determined, the achievement of
which signals a certain anomalous radiation situation and is, if
necessary. an instruction to initiate appropriate radiation
protection measures. Three types of reference levels are
introduced :
Radiation monitoring usually consists of three parts: monitoring of persons, monitoring of the workplace, monitoring of radioactive waste and possibly. monitoring the surroundings of the workplace with ionizing radiation.
Personal
monitoring - personal dosimetry
Personal monitoring consists in measuring the personal
radiation doses of individual radiation workers,
whether it is external radiation or o internal
radiation from radioactive contamination. Monitoring of
external radiation is performed using personal dosimeters
, which radiation workers wear during all work with ionizing
radiation and stay in the controlled zone. These dosimeters are
centrally evaluated at specified time intervals (usually 1
month), resulting in dose values (in mSv).
Note: It should be noted that direct
measurement of the absorbed dose is very difficult, apart from
laboratory methods, generally dosimetric quantities are
not directly measurable. Doses are determined indirectly
and approximately, based on certain model assumptions. The
surface dose and the dose at a certain depth are derived from the
data on the dosimeters.
The following types of personal dosimeters
are used :
Radiation monitoring of the
work and environment
In order to ensure the optimal level of radiation protection
and radiation prevention, it is important to monitor the
intensity of ionizing radiation and, if necessary. the presence
of radioactive contamination in the premises of workplaces, their
surroundings and in the environment of the population - the
so-called radiation monitoring .
..........................
Dose and dose rate measurement in laboratories,
examination rooms and inpatient wards. Workplace monitoring
program system ........................
5.5.
Open radionuclides. External and internal contamination
Closed
and open emitters
In terms of material nature and technical design, sources of
ionizing radiation are divided into two groups :
For the classification of emitters
according to activity in relation to radiohygienic risks, the
so-called exemption level of activity is
introduced : it is a value of total activity (or specific mass
activity) at which radiation risks and radioactive contamination
are not considered negligible (compared to natural sources of
radiation). Such a emitter is not subject to radiation protection
regulations and we could have it without risk, with a little
exaggeration, even at home in the living room ...
According
to the severity of radiation risk, sources of ionizing radiation
are divided into 5 categories :
Insignificant sources
(eg small closed standards for spectrometric calibration ,
ionization fire detectors, radioactive substances with activity
lower than the exemption level, etc.);
Small resources
(such as stronger closed emitters and low open activities);
Simple sources
(eg X-ray diagnostic devices and defectoscopic devices);
Significant sources
(eg closed emitters for radiotherapy, accelerators, highly active
open emitters); and finally
Very significant sources
(such as nuclear reactors or radionuclide production facilities).
Laboratory work with open radionuclides
and their storage, radioactive waste, application of
radionuclides to patients.
Radiation hygiene when using open emitters -
protection of workers from external radiation and internal
contamination .
Radioactive
contamination
When handling open radioactive substances, their leakage and
subsequent contamination (pollution) of objects, the working
environment and persons with these radioactive substances can
occur . Contamination can be superficial external and internal .
Surface contamination
Surface contamination of work surfaces, aids, clothing or people is most
common . Surface contamination can lead to higher doses of radiation, especially on contaminated areas
of the skin, but in some cases can also result in internal
contamination, see below. For continuous control of surface
contamination during and after work, radiometers with large-area probes are used,
which should be located in all exposed workplaces and in hygienic
loops.
Sensitive methods contamination controls is the method of dross, when wiping with a cotton
swab dipped in a suitable solvent (alcohol gasoline) or.
contamination from a defined area of the exposed site and then
measure it in a test tube with a well scintillation detector.
Decontamination
In the event of contamination of the working environment, it is necessary to prevent the spread of contamination, mark a visibly contaminated area, report this incident to a manager or supervisor
and cooperate in decontamination under his guidance . When
decontaminating, it is necessary to first aspirate
as much of the
active liquid as possible with filter paper or pulp and then wash and wipe the contaminated area with a suitable cleaning
or decontamination agent. Generated waste
it is necessary to
store in plastic bags and contaminate contaminated objects or
store them in plastic bags for radiation . Contaminated
water must be
poured into the waste connected to the extinction sumps. The
effectiveness of decontamination is continuously checked by measuring
with a radiometer. If the activity cannot be completely
eliminated, the site should be marked and covered with protective
paper or foil; the manager or supervisor will then decide on the further
procedure and resumption of operation .
In the event of personal contamination , the worker must remove contaminated
clothing or protective equipment, check the contamination of the
body surface and, if necessary, clean it by washing or showering. m. It is also necessary to check whether
there has been any internal
contamination of the worker. In cases of suspected internal
contamination and exceeding the maximum permissible dose of
radiation is necessary to take the necessary health measures in cooperation with SÚJB and sanitary
authorities, including d oèasného removing the worker
from the environment with ionizing radiation.
Extensive
radioactive contamination is already a radiation accident
- see the following §5.6.
Internal contamination
When handling higher activities of open emitters, unwanted
penetration of radioactive substances into the body can occur
- internal contamination and subsequent internal
irradiation. Note: A
special case of "internal contamination" is the
deliberate application of a radioactive
substance - a radioindicator , a radiopharmaceutical
- to an organism for the purpose of diagnosis or
therapy in nuclear medicine (" Scintigraphy ", " Radioisotope Therapy ").
Upon entry into the body, the radioactive
substance enters the metabolism and can be distributed
in individual tissues and organs depending on their chemical
composition - part accumulates in the so-called target
organs , the rest is distributed throughout the body.
Most of the radioactivity is then metabolized
and after a certain time it leaves the body (mostly in the urine, to a lesser extent in the faeces,
sometimes in sweat or exhaled air) .
However, part of the radioactivity may remain permanently
bound (eg iodine in the thyroid gland, strontium or
plutonium in the bones, cesium in the muscles, ...) - it is retention
(lat. Retineo, retentum = retain )
. Due to inhomogeneous distribution
of radioactive substances in target tissues and organs, the
internal irradiation of the organism may be highly heterogeneous
(see below " Determination of the radiation dose from
internal contamination. MIRD method ") .
Radioactive contamination can enter the
body in basically four ways :
When a radioactive substance enters the body through ingestion or inhalation, the substance passes relatively quickly from the digestive tract or lungs to the blood and lymph. Its other behavior - distribution, metabolism, persistence or excretion from the organism - is determined by the chemical properties of the substance and the rate of radioactive conversion of the radionuclide.
Monitoring internal
contamination
Determination of internal contamination g -radionuklidy be p rov EST external measurement of gamma
radiation using a sensitive scintillation detector above the
critical (target) organs. E.g. u 131 I is a thyroid gland, so in workplaces
performing thyroid therapy with radioiodine,
it is necessary to
periodically measure the activity of the thyroid gland in all
workers involved in these therapies. A
special method of measuring internal contamination is the use of whole-body
detectors radiation, equipped with scintillation or semiconductor
detectors, which are installed in some workplaces with high
radioactivity (nuclear reactors, production of radionuclides) and
risks of internal contamination - Category IV workplaces. These
methods of external monitoring are mainly used
for internal contamination by radionuclides emitting g radiation , which
penetrates the tissue out of the body. For clean emitters b , external
monitoring can only be used if, due to the high energy, the
electrons b generate harder bremsstrahlung radiation in the tissue
(eg 32 P
or 90 Sr- 90 Y), which penetrates
the tissue out of the body. For low energy radiators bit has low
intensity and energy braking radiation, it does not penetrate out
of the body and external detection cannot be used.
Another method of monitoring internal
contamination is to measure the activity of
blood and urine samples.
Determination
of radiation dose from internal contamination. MIRD method.
During external irradiation of the organism, the energy
of radiation is transferred to the tissues and organs only for
the time when the body is exposed to radiation. If the
radionuclide enters the body, it remains deposited there
and irradiates it for a long time. Irradiation is heterogeneous
and changes over time as the radionuclide moves and distributes
in the body, is excreted from it, and decreases in radioactive
transformation. It is generally a complex function of
time and space .
Accurate determination of radiation doses
in individual tissues and organs during internal radioactive
contamination is therefore generally a very complex and difficult
task. The absorbed dose depends not only on the physical
characteristicsradionuclide (types and energies of
emitted radiation, half-life), but also on its chemical
form (and very significantly!), normal or pathological pharmacokinetics
- rates of accumulation and excretion of the substance in organs,
on anatomical factors (sizes, distribution and
densities of organs and weaving).
A more detailed analysis of dose
distribution in tissues and organs will be provided below. In
terms of risk for stochastic effects are approximate and global
assessment of the radiation load from internal contamination uses
so called. Conversion factor radiological
contamination hour [Sv / Bq] is a coefficient indicating the effective
dose in the body (ie. Time effective dose), caused
by the uptake of a unit activity of 1Bq (usually
1MBq) of a given radioactive substance into the organism. The
values ??of the conversion factor depend not only on the type of
radionuclide, but also on the compound in which the radionuclide
is present and on the way in which the radionuclide has entered
the organism; values ??for ingestion h ing and for inhalation
h inh are
most often given . Conversion factors are given for the so-called
" reference person " with anatomical and
physiological characteristics typical of the average population,
eg weight 70 kg. More accurate dose values ??from internal
contamination are determined based on the following MIRD models :
Radiation dose D
[Gy] in the organ in which the radioactive substance is contained
(assuming an even distribution for simplicity) is given by the
product of two quantities
D
= S. A S :
¨ The accumulated
activity of A S indicates the total number of radioactive
transformations that take place in the considered organ during
the entire presence of the radionuclide. Activity accumulated
value A S Determine the integral or area under the curve of time
vs. activity, and the institution from time t = 0 entry
radionuclide to the complete disappearance of (theoretically up ¥ ) A S = 0 ò
¥ A (t) dt (middle
part fig.5.5.1).
The excretion of a given
radioactive substance from the organ (or the whole body) has an
approximately exponential time dependence and
its rate is characterized by the so-called effective
half-life T 1/2 ef . The effective half-life is due to a combination of a
physical half-life T 1/2
phys particular
radionuclide and called. Half life T 1/2 Biol ,
i.e. the time required to eliminate half quantity is absorbed by
the substance metabolism. The effective half-life is then T 1/2 ef = T 1/2 biol .T 1/2 phys/ (T
1/2 biol + T 1/2 phys .). For the kinetics of radionuclides in tissues and
organs, the biological half-life of excretion is usually
dominant, which is usually significantly shorter than the
half-life of the radionuclide itself.
¨ The dose constant S
represents the dose related to the unit activity of a given
radionuclide in the organ [Gy / Bq] (in
practice [mGy / MBq]) . The constant S
includes the influence of all types of radiation emitted by a
given radionuclide - particles b a a , radiation g , characteristic
and braking X-rays, convective and Auger electrons.
Alpha and beta particles (as well as
conversion and Auger electrons) are completely absorbed in the
source organ and contribute only to the dose in this organ, which
in this case is D = E a,
b . A S / M, where E a, b is
the mean energy of the emitted particles a or b , AS is the
cumulative activity, M is the mass of the organ or tissue
(the dose constant is therefore S = E a, b / M in this
case ). The basic relation for the radiation dose from the
homogeneous distribution of radioactivity in the substance was
derived above in §5.1, passage " Radiation dose from radioactivity ".
Penetrating gamma and X radiation can also
radiate into the surrounding tissues and organs (Fig. 5.5.1 on
the left). Its contribution to the constant S depends on
the energy of the radiation, the distances, the size and shape of
the source and target organs, and partly on the type of tissue
between them.
Dose constant values for
individual organs and radionuclides are determined using
microdosimetric methods including phantom modeling and
simulation; in the simplified version, they are given in the
radiation protection tables (these are average values ??based on
a person weighing 70 kg).
Fig.5.5.1. Left: Source and target organs in the
body. Middle: Time dependence of activity in
source organs. Right: Time dependence for
determination of doses from internal contamination by MIRD
method.
The figure roughly simulates the situation
after the penetration of radioiodine 131 I into the organism. Radioiodine is rapidly taken up in
the thyroid gland, then metabolized and excreted by the kidneys
into the bladder, from where it periodically leaves the body
during urination.
The tissue or organ in which we
need to determine the radiation dose is called the target
, other organs and tissues in the body are considered to be the source
for it - the left part Fig.5.5.1. The radiation dose D T in target organ T
is the sum of doses from the " own "
the cumulated activity A S
T
contained in the body and the dose contributions penetrating
radiation of activity and S
and
accumulated in the surrounding organs source:
D
T
= S T . A T S
+ i = 1 S N (S i .A S i ) ,
where S i
are the dose constants for target organ irradiation from activity
A S i contained in the
surrounding organs "i" (which are the source for target
organ T ; in general, each organ can be considered as both
a target and source for other bodies). The constants S i include, but are not
limited to, the absorption of radiation in tissues and the
decrease in radiation intensity with distance. In the first
approximation, the proportionality S i ~ e - m .d / d 2 , where m (E g , r ) is the linear
tissue attenuation factor of density r for radiation of energy E g , d
is the distance of the source organ from the target organ.
However, the precise calculation should include integration
across the entire space between the source and target organs, as
well as across the actual volume of both organs.
A complex method, including the
above-mentioned physical and biological factors for the
determination of radiation doses in individual organs from the
internal distribution of radioactive substances, is called MIRD
( Medical Internal Radiation
Dose). The basic MIRD method uses some flat-rate
data on anatomical conditions in the so-called "standard
human" weighing 70 kg. The refinement of these data can be
achieved by using volummetry on density X-ray CT
images - the so-called voxel method
. And the specification of specific data on the distribution and
pharmacokinetics of a given radioactive substance can in
principle be obtained by means of quantitative
scintigraphy . Such an improved, so far the most complex
and most accurate method of determining radiation doses in organs
and tissues in 3D radiopharmaceutical dosimetry, is important in
planning and monitoring the course of radionuclide therapy in
nuclear medicine - a more detailed analysis is given in the
section " Radioisotope therapy"Chapter 3" Application of ionizing radiation.
"It should be noted that due to the significant variability
of biological factors in particular, even when the inclusion
complex mentioned methods can not achieve a high accuracy
determination of radiation doses in organs - the error is about
30% or above.
In practice, the final dose from the
target organ's own accumulated radioactivity is
dominant for the resulting radiation dose in the target organ ,
while the contribution from other more distant source organs is
usually negligible, especially if the radioactive substance is
pure emitter b (or a ) or the penetrating g-Radiation is not high. And so it is in the vast
majority of cases of radiation-significant internal
contamination, including the application of radiopharmaceuticals
in nuclear medicine.
5.6.
Radiation protection at workplaces with ionizing radiation
(Categories of workplaces, controlled zone, storage and disposal
of radioactive waste.)
Organization
of workplaces and their categories
The construction, layout and equipment of workplaces must be
carried out in such a way as to ensure sufficient radiation protection of workers, other persons and the
environment. In the event of an accident, it must be possible to
decontaminate people and the workplace as quickly and efficiently
as possible.
Workplaces are divided according
to whether they are designed to work with closed emitters (such
as radiological or radiotherapy workplaces) or with open
emitters. According to the severity of the radiation risk,
workplaces are divided into 4 categories, for workplaces
with open emitters it is according to the processed
activities.
¨ Work I. Category are for working
with low activities Radion cleaning
with low radiotoxicity (minor source IZ) and after the
construction or equipment does not differ from conventional
chemical laboratories.
¨ Category II workplaces process medium activities of open
radionuclides, they have a controlled zone
and are equipped with protective
equipment incl. hoods, or there is a separate sewer for active
waste.
¨ Category III workplace is designed for demanding work with strong
sealed emitters (accelerators, irradiators in radiotherapy and
industry) and with high activities of open radionuclides (eg
radioiodine therapy, uranium ore mining and processing,
radiochemical plants). Therefore, considerable requirements are
placed on its construction and equipment in order to ensure the
fastest and most effective cleaning in the event of
contamination. There should be 3 types of rooms in the controlled
area: for demanding work with high activities ("hot"
operations), for routine laboratory work and measuring
rooms. In addition, a
special room or to the rectory
for storage of radionuclides and radioactive wastes. Floors and walls
of laboratories must be smooth and washable, floors are further
sloped and provided with waste. Intensive ventilation with active
air filtration with an outlet above the roof should also be
provided . Liquid radioactive
waste is led to extinction tanks . The workplace must be equipped with
suitable shielding, manipulators, fume hoods and devices for
protective dosimetry. The controlled zone should be separated
from other areas by hygienic
loops with a radiometer for
checking or contamination and with the washroom.
¨ Category IV of workplaces
is designed for nuclear reactor operations , radionuclide production and
radioactive waste repositories with high activities and long half
- lives are included. In addition to irradiation and
contamination directly at the workplace, there is also a risk of
environmental contamination ,
which implies the need for radiation monitoring of
the workplace.
Controlled zone
The radiohygienically controlled zone is called those areas of the
workplace where ionizing radiation ( radioactive substances or other
sources of ionizing radiation) is handled and where the regime
of protection of persons against ionizing radiation must be
observed *) . Entrances to the controlled
area must be marked
with warning signs. Only trained
radiation workers equipped with protective equipment and personal
dosimeters have free
access there , other persons only accompanied by radiation
workers and their stay is registered.
*) The current
radiation protection standards
specify: " Controlled zoneis defined wherever it is expected that
during normal operation or with foreseeable deviations from
normal operation, the radiation dose of workers could exceed 3/10
of the limit for radiation workers ".
In some workplaces, especially I. category, the so-called monitored
zone , which is an area
where, during normal operation of radiation sources, the
radiation dose could exceed the general limits for the
population.
Radiation
accidents and crashs
Every human activity - in industry, transport, agriculture,
health, science and technology, laboratory work, as well as in
everyday life, sometimes "fails", breaks, breaks - an accident occurs . Of course, this can also happen
in workplaces with ionizing radiation. By radiation
accident we
mean an unplanned event that will increase the danger of people from ionizing radiation. In workplaces with closed emitters, it is mainly about
unwanted exposure of people . In workplaces with open emitters,
it is mainly an uncontrolled leakage
of radioactive substance into the working environment (eg by
spilling, spraying, breaking the bottle with the radioactive
solution, etc.) with subsequent contamination
of the
working or environment or workers. Such events
can occur when
handling open emitters in the process of their preparation,
transport, storage, application and
disposal.
For radiation accidents (especially minor ones), the
name emergency is sometimes used . The extent of
a radiation accident or emergency varies 1.-3. severity
:
An international 7-level table
is also used to evaluate radiation accidents in nuclear reactors
: 1st stage = deviation from normal operation; 2nd degree =
fault; 3rd degree = serious disorder; 4th degree = accident with
effects in a nuclear installation; 5th degree = accident with
effects on the environment; Stage 6 = accident with serious
radioactive consequences; Level 7 = major accident with extensive
radioactive consequences.
Below are some
examples of more serious radiation accidents.
Nuclear
accidents and disasters with open emitters
One of the typical situations where a serious radiation accident
with open emitters can occur is careless work with fissile
material (especially uranium 235 U or plutonium 239 Pu), especially if it is in higher concentrations - it
is the so-called enriched. If a larger amount of such material is
available, the critical amount may be exceeded
and a chain fission reaction may be triggered, producing a very
strong flash of neutron radiation and g radiation
, followed by high contamination with
fission products. Persons at the scene of an accident receive
very high doses of radiation, often lethal.
Several accidents of this kind have happened in laboratories and
nuclear plants.
More recently, for example, there was an
accident at the Tokai-Mura nuclear enrichment
plant in Japan on September 30, 1999. Here, 3 workers prepared
nuclear material in a solution of uranium oxide (enriched to more
than 18% 235 U) and nitric acid. Inadvertently, more uranium
solution was added to the reaction vat, resulting in a
supercritical amount. A bluish flash signaled the ignition of the
chain reaction. Two workers standing closest died, a third worker
was being treated for an acute radiation sickness.
A number of radiation accidents have
occurred at nuclear reactors . A moderate
accident (level 5) occurred on March 28, 1979 inThree Mile Island nuclear
power plant on River Island near Harrisburg
, Pennsylvania in the USA. Due to a failure of the
secondary cooling circuit pump, the temperature and pressure in
the primary circuit increased, the pressure relief valve opened
and the reactor was stopped in an emergency. However, the safety
valve blocked in the open position, the pressure in the primary
circuit dropped, some spare water cooling pumps failed, the
remaining heat began to boil the water, and several fuel cells
were leaking. Radioactive water, steam and gases leaked into the
surroundings - a wide area around the power plant was infested
, and several thousand people were evacuated. As later in
Chernobyl, the perpetrators kept the accident completely hidden
for several days; however, unlike Chernobyl, the circles
concerned later succeeded in the real extent of the accidentconfidential
, so that reliable data on the amount of radioactive material
leaked are lacking.
Accident at Chernobyl
The most severe radiation accident to date (7th
degree) occurred on April 26, 1986 at the Chernobyl
nuclear power plant (the principle of operation
of nuclear reactors and their safety is briefly discussed in
§1.3 "Nuclear reactions", section " Fission
of nuclear nuclei "; and the
causes of the Chernobyl accident are described in the section
" Chernobyl nuclear reactor accident "). During the destruction of the nuclear reactor,
there was extensive contamination of the
environment with radioactive fission products and the exposure of
232 people with high doses of radiation (units
up to tens of Sv), associated with deterministic effects and
acute damage to health; in 31 cases there were even lethal
effects (of which 2 workers were killed directly when the reactor
exploded, but even if this did not happen, they would receive a
lethal dose of radiation)! Many hundreds more people received a
radiation dose of tens to hundreds of mSv, for which an increased
incidence of stochastic effects can be expected (by at least 1%;
although it has not yet been confirmed ...).
Fortunately, despite the seriousness and local
tragedy of the Chernobyl accident, its consequences turned out to
be significantly smaller than they initially
seemed. And, of course, many times smaller (at least 100 times
smaller!) Than claimed by some propaganda materials, manipulated
for political reasons(Cold War -
anti-communism, anti-Sovietism) , or from
the motives of particular interests (fight
against nuclear energy, coal lobby, etc.) .
In any case, the Chernobyl accident has become a milestone
in nuclear energy and radiation protection. It led to a
substantial tightening of safety regulations and
standards of radiation protection not only in nuclear energy, but
in the whole area of ??ionizing radiation applications (this resulted in excessive bureaucratization of
radiation protection - cf. the section " Bureaucratic
requirements for radiation protection " in §5.8) . An accident as
large as in Chernobyl will probably never happen again
!
Another recent major nuclear
accident in Japan is briefly described in the section " Accidents at the Fukushima Nuclear
Power Plant ". No one was to blame
for this accident, it was caused by a huge natural disaster. It
has also been formally rated 7, but this is misleading, as its
scope and severity are incomparably smaller than at Chernobyl.
In large radiation
accidents with extensive radioactive contamination of the
environment, the main health risks and injuries in the majority
of the affected population are often caused not so much by
radiation as by stress from evacuation and concerns arising from
overestimation of risks, radiophobia ...
Radiation
accidents with closed emitters
Even with closed emitters , serious radiation
accidents can occur if their radiation intensity (dose rate) is
appropriately high. Potentially dangerous emitters from this
point of view are particularly strong radiotherapeutic
irradiators or industrial emitters, eg
for defectoscopy or sterilization. Careless handling of such
unprotected emitters can result in external exposure of
the body to high radiation doses either whole
body ( Þ radiation sickness - sometimes lethal, increased
incidence of stochastic effects) or locally ( Þ radiation burns).
A tragic radiation accident of this kind
happened in September 1987 in the city of Goiania
in the Goias region of Brazil, where a cesium emitter 137 Cs with an activity
of about 50,000 GBq was unprofessionally and uncontrollably
removed from a radiotherapy irradiation intended for disposal .
Ignorant workers took it home, dismantled it and then sold it for
scrap. The workers of the waste storage warehouse also
distributed the radiator and took its individual parts home (they
liked the bluish fluorescence!), Even children played with them.
The result was 5 deaths from radiation sickness, 20 people had
local radiation burns (mostly on their hands).
Other radiation accidents, some with lethal
consequences, occurred during the theft of emitters. There are
even several known cases of criminal abuse of emittersagainst
persons (murder or attempted murder). The perpetrators and
victims of these radiation scenes are mostly those involved in
espionage activities and organized crime.
Many radiation accidents have become overexposed
to patients during radiotherapy due to incorrect
calibration of the irradiator or an error in the irradiation
plan. A serious accident of this kind happened in December 1990
at the University Hospital in Zaragoza, Spain, where poor
calibration of the linear accelerator caused 2-7-fold
overexposure of irradiated patients, as a result of which 18
patients died from radiation and another 9 suffered radiation.
damage.
It should be noted with satisfaction that radiation accidents are relatively rare at present . The field of applications of ionizing radiation is monitored, coordinated and secured as thoroughly (sometimes perhaps overly bureaucratically ...) , like perhaps no other field of human activity. Mostly professionally founded people work here, well acquainted with the principles of working with radioactivity and ionizing radiation as well as with the principles of radiation protection.
Radioactive waste
Radioactive waste is such an unusable
*) material (substance or object) generated during the production and use of
radiation sources that contains radioactive substances. According
to the above classification of radioactive emitters, these emitter wastes are open . Radioactive waste can be
potentially dangerous for the environment - it can
cause unwanted radiation or contamination.
*) However, this unusability may be relative and conditioned by the current
state of technology. With the development of new technologies,
initially difficult waste may become a welcome
raw material
(see, for example, the section " Nuclear
waste " in
§1.3).
How can
radioactivity be destroyed ?
It is known that almost all
pollutants can be eliminated by incineration -
at high temperatures above about 600 ° C chemical bonds break
down, oxidation occurs and the substance ceases to be toxic (with
some exceptions are heavy metal compounds, which are sometimes
difficult to convert to harmless compounds). This does not apply
to radioactive substances - the actual radioactivity cannot be
destroyed by incineration! - see
the passage " Independence of radioactive decay on
external conditions " in chap. 1.2 " Radioactivity ". By normal incineration we only
break down or change the chemical bonds, but the number of
radioactive atoms remains exactly the same as before incineration
- some of them escape in gaseous form in smoke, some remain in
the solid phase in the ash. To destroy radioactive nuclei, we
would have to heat the substance to a temperature of several
million degrees for nuclear reactions to occur. In this way, we
could destroy existing radioactive nuclei, but in nuclear
reactions, on the contrary, new radioactive nuclei could be
formed from originally inactive nuclei ... In §1.3 " Nuclear reactions " the so-called transmutation technologies
of neutron radiation disposal ( ADTT )
are discussed , which may be relevant for long-lived and highly
active waste from nuclear reactors.
The activity and half-life of
the relevant radionuclides, as well as the chemical form
, are decisive for the handling and disposal of
radioactive waste . Depending on the half-life and radiotoxicity,
a so-called release level is set for each
radionuclide (or category of radionuclides) : it is the value of
activity (total or specific weight or
volume activity) below which the risk of
contamination is negligible and the substance can be released
into the environment without special radiohygienic measures. The
value of the release level is determined on the basis of the
limitation of the possible radiation exposure during internal
contamination by a given radionuclide, using the conversion
factors of ingestion and inhalation.
(analyzed above in section " Determination of radiation dose from
internal contamination. MIRD method. "). ........ add categories of radionuclides
......
Depending on the state,
radioactive waste can be solid , liquid or gaseous
:
From the point of view of radiation
protection, it is therefore necessary to
keep
radioactive waste under control until its radioactivity drops to
a sufficiently low level due to spontaneous decay, so that no
threat to the biosphere can occur. This is a difficult problem
for highly active wastes containing radionuclides
with long half- lives; this category mainly
includes spent nuclear fuel from fission nuclear reactors (§1.3, section " Nuclear
waste ") .
Another possibility
is the controlled slow long - term introduction of
radioactive substances into the natural environment ,
when two conditions are met :
1. The
current release level of radionuclides must not be exceeded in
order to avoid the possibility of increased radiation exposure
locally at the point of discharge.
2. The total amount of radioactive substances
released must not exceed the "volume capacity" of the
volume of distribution of those substances in nature, so as not
to increase the natural background radiation in the future.
5.7.
Radiation exposure during radiation diagnosis and therapy
Radiation exposure from diagnostic medical examinations is
generally low and is
almost always justified by the benefit of
accurate diagnosis of possible health disorders and pathological
conditions. These exposures are usually comparable to the doses
we receive continuously from the natural radiation background all
around us. There is no direct evidence that these low radiation
doses could be harmful *) - despite a hypothetical linear
threshold-free dependence and a number of more or less misleading
tables in the radiation protection literature (such as comparisons of radiation and smoking) . In contrast, the benefits of a
medical examination are unquestionable and can be very healthy
significant !
*) The issues of the radiobiological effect
of low doses of radiation are discussed above in §5.2, section
" Relationship between dose and
biological effect ",
section " Problems
of very low doses - are they harmful or beneficial? ".
The
therapeutic use of radiation naturally leads to higher
exposures , at which it is necessary to consider and
optimize the risks of treatment against the possible benefits.
However, even here, with proper planning, optimization and
strategy, the health benefits are often
unquestionable.
Despite the predominant health benefits of
ionizing radiation applications in medical diagnostics and
therapy, issues of radiation protection must be given due
attention here as well!
Radiation
doses and patient protection during diagnostic and therapeutic
procedures
Medical diagnostics and therapy are among the most important
applications of ionizing radiation; it also contributes the most
to the radiation exposure of the population from all artificially
created radiation sources.
The methodology of radiation protection in
medical applications of ionizing radiation - in X-ray
diagnostics, radiotherapy and nuclear medicine - is generally
based on the basic principles of radiation protection mentioned
in §5.3 " Objectives and methods of radiation
protection ", but has its
significant specifics. In particular, there are no
binding exposure limits so as not to
limit certain diagnostic and therapeutic procedures necessary to
ensure the health or life of patients. The slogan is used with a
bit of exaggeration: "Each patient will receive
a radiation dose deserves ": the dose needed
for accurate diagnosis or effective treatment. Instead limits are
determined a recommended value of benefits
called. guideline values - reference levels
, as a guideline for implementing specific diagnostic or
therapeutic methods(see below "
principle of optimization ").
The principle of
justification of medical exposure
Radiation protection of patients is based
on the ethical requirement that the risk
of radiation
damage in diagnostických or therapeutic
procedures were
exported (or better if possible
overridden ) expected
health benefit to the patient. This
basic requirement in the medical application of ionizing
radiation is called the principle of justification of
medical exposure in radiation protection .
Optimization
principle
Another important aspect that contributes in practice to the
balance of radiation risk and benefit is the analysis of
radiation protection optimization. In X-ray diagnostics, we will use the
lowest exposure that will ensure quality
and well-evaluable images , not a higher exposure. When diagnosing in
nuclear medicine, it is necessary to apply only
such a necessary amount - activity - of radioactive substances (required qualities and purity), which guarantees sufficient
diagnostic information in the images with the lowest
possible radiation exposure of the
patient.
To optimize the amount of applied
radioactivity of various radiopharmaceuticals for individual
examination methods, tables of guideline values , also
called diagnostic reference levels ,
were prepared , which also allow recalculation of applied
activity for individual patients, mostly according to patient
weight (even non-standard - eg children, overweight etc .).
Radiation exposure of patients from X-ray
examinations
By far the most common exposure to ionizing radiation (from artificial sources) in
humans is X-ray diagnostics . In earlier times (around the 60s-70s of the 20th century) , when skiagraphy was performed on X-ray films and
sciascopy through fluorescent screens (amplifying
foils and image intensifiers were not yet widespread, digital
flat-panels did not yet exist) , the doses
were from X-rays often many tens of mSv. After all, they were not
even determined at that time ...
With the development of amplifying foils,
image amplifiers and especially digital display electronic
flat-panels (see §3.2, passage " Electronic
X-ray imaging ") radiation doses from X-ray examinations decreased
significantly , in simple images they represent only tenths to
units of mSv. Relatively higher doses (up to tens of mSv) arise
in CT examinations of larger areas (whole chest, abdomen, whole
body), which is, however, balanced by the greater complexity of
diagnostic information. Also, high doses arise during complicated interventional X-ray-guided procedures (here, in addition, the doses are highly variable,
depending on the complexity of the procedure and how easy or
difficult it is for the given patient to "perform" the
procedure) .
Absorbed radiation dose D
[mGy] in the X-ray examination of a certain area is basically
given by the product of the intensity of X-rays (this is given by
the X-ray current [mA]), the exposure time [s] and the
corresponding coefficients :
D
= G. mA s .
The product of the current I and the exposure time t
indicates the electric amount Q - the total charge
of the electrons - which flowed through the X-ray during
the exposure Q = I. t [mA.s] -
[miliCoulomb] . The electric amount Q
determines the total number of X-rays emitted by the X-ray, and
thus the signal strength during X-ray imaging.
Coefficient G it includes a number
of factors, such as the efficiency of X-ray production by X-rays,
its energy given by the voltage [kV] for X-rays, filtration,
distance, tissue absorption coefficients. It is measured using
phantoms, most often water-filled "aquariums" (for
planar X-rays), or cylinders with a diameter of 16 cm (head) or
32 cm (chest) for CT, equipped with ionization chambers,
thermoluminescence or semiconductor detectors. The probability of
biological stochastic effects is proportional to this absorbed
radiation dose [mGy] and the size
(volume) of the irradiated area [cm 3 ]. This size - volume - is approximately proportional
to the irradiated area [cm 2 ] in the planar image, or the length [cm] of the CT
scanned area.
In the planarX-ray
diagnostics, this is quantified using the area dose
quantity DAP ( Dose Area Product )
[Gy.cm 2
], which is the product of the input dose of X-rays and
the size - area S - of the irradiated field: DAP = D. S.
The effective dose D ef [mSv] for a patient, expressing the stochastic effects
of radiation on the organism as a whole, is then calculated as
the product :
D
ef = E DAP . DAP ,
where the coefficient E DAP ( regionally normalized effective dose ) [mSv
Gy -1 cm -2 ] includes the
averaged tissue (organ) weighting factors w T for structures in the
irradiated area (§5.1 "Basic
quantities of dosimetry", passage " Effective
dose ") . Specific DAP
values during X-ray examinations are measured using thin
plane-parallel ionization chambers mounted on the output
collimator of the X-ray device - so-called DAP meters
or KAP meters (§3.2,
section " Radiation load during X-ray
examinations ") .
Typical exposures for planar X-rays in AP
projection are approximately: head 25mAs, DAP = 1Gy.cm 2 ; chest 30mAs, DAP =
0.6Gy.cm 2
; abdomen 60mAs, DAP = 1,8Gy.cm 2 ; pan 60mAs, DAP = 2Gy.cm 2.
During the CT
scan, the X-ray circle rotates around the imaging area and
irradiates it on all sides with a substantially uniform dose
within each section. The examined area can be approximated in
terms of dose by a cylindrical shape of
a certain diameter and length. For CT, therefore, dose D
is measured by an ionization chamber inside an acrylate
cylindrical homogeneous phantom with a diameter of 16 cm for the
head and 32 cm for the body and is quantified using the dose
rate index CTDI ( CT Dose Index ) [mGy], with resp.
correction for the pitch factor for spiral instruments.
This dose value determined at the center of the cut is considered
to be an objective indicator ( index) doses in tissue.
Here, the probability of biological stochastic effects is again
proportional to the absorbed radiation dose
[mGy] and the size of the irradiated area,
proportional to the scan length
[cm]. The X-ray CT diagnosis is expressed by the resulting
linear dose DLP ( Dose Length Product )
[mGy.cm], which is the product of the absorbed dose D
and the length L irradiated area: D = DLP . L (= CTDI. L).
The effective dose D ef [mSv] for a patient, expressing the stochastic effects
of radiation on the organism as a whole, is then calculated as
the product of :
D
ef = EDLP . DLP ,
where the coefficient E DLP ( regionally normalized effective dose ) [mSv
mGy -1 cm -1 ] includes averaged tissue
(organ) weighting factors w T for structures in the irradiated area (§5.1 "Basic quantities of dosimetry",
passage " Effective dose ") .
Typical dose
parameters for CT imaging at 120kV and exposure to 200-400mAs are
approximately: head CTDI = 45mGy, DLP = 640mGy.cm; chest CTDI =
15mGy, DLP = 400mGy.cm; abdomen, pelvis CTDI = 17mGy, DLP =
700mGy.cm.
Using special body
modeling anthropomorphic phantoms, empirical data and
computer simulations, the following approximate values of E DAP and E DLP coefficients were
determined for the basic examined areas of the human body :
Investigated area: | head | neck | thorax | belly | pan |
E DAP [mSv Gy -1 cm -2 ]: | 0.04 | 0.07 | 0.15 | 0.18 | 0.20 |
E DLP [mSv mGy -1 cm -1 ]: | 0.0023 | 0.0054 | 0.017 | 0.017 | 0.019 |
Tab.5.7.1. Approximate values of the E DAP and E DLP coefficients for the basic imaging areas. |
Note: The radiation
dose in planar X-ray imaging (as opposed to CT) for individual
examined areas is significantly dependent on the geometric
projection used. In our illustrative table, wehave given
approximate values ??forE- DAP for antero-posterior AP projection.
Current
computer-controlled X-ray devices (especially CT) determine
andrecord the DAP, CTDI and DLP values when imaging a specific
patientin the result protocol (in DICOM
format). The effective dose D ef [mSv] can then be
easily determined by multiplying the value of DAP or DLP by the
appropriate coefficient E DAP or E DLP ; in the case of multiple area investigations, the
total dose is E efgiven by the sum over all examined parts of the
patient's body. This simple method of determining the effective
dose from an X-ray examination is quite sufficient
for the purposes of radiation hygiene - even more complex methods
do not provide more valid results. Indeed, as noted in §5.1, the
very concept of effective dose is only averaged,
rough and simplified " reasonable estimate
" of complex and individually dependent processes of the
biological effects of radiation ...
In terms of optimization of radiation
protection for X-ray examination were fixed guide values - Diagnostic
Reference levels - recommended exposures for planar
skiagraphic images and CT imaging :
Planar skiagraphic images | CT scan | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
Tab.5.7.2. Diagnostic reference levels of recommended exposure for planar skiagraphic images and CT imaging |
Patient
radiation dose from radionuclide examinations
is basically determined by the applied activity
[MBq] radiotracer (direct proportion) half-life of
the radionuclide used, type and energy of
radiation emitted, and pharmacokinetics
radiotracer - degree of accumulation of the
radiopharmaceutical in various tissues and organs, as well as its
rate of biological excretion (excretion) or the residence
time of the radiopharmaceutical in the tissue. These
dependencies are quite complex and individual, in full complexity
the MIRD method
discussed above tries to solve them , Fig.5.5.1.
Based on this method, as well as empirical
determinations and estimates, tables of conversion
factors - conversion factors h [mSv /
MBq] for individual radiopharmaceuticals were compiled , which
allow by simply multiplying the applied activity A [MBq]
to approximately determine the effective dose D ef [mSv] for patient: D
ef = h. A.
The values ??of conversion factors h (effective
doses / 1MBq) and guideline values - diagnostic
reference levels - recommended applied activities (normalized to the patient's weight of 70 kg) for some more frequently used radiopharmaceuticals in
scintigraphy are given in the following table :
Radionuclide | Chemical form | Effective
dose h [mSv / MBq] |
Type of examination | Applied activity [MBq] |
||||||||||||||||||||||||||||||||||||||||
99m Tc |
|
|
|
|
||||||||||||||||||||||||||||||||||||||||
131 I | iodide | 24 | thyroid | 15 | ||||||||||||||||||||||||||||||||||||||||
123 I |
|
|
|
|
||||||||||||||||||||||||||||||||||||||||
111 In |
|
|
|
|
||||||||||||||||||||||||||||||||||||||||
67 Ga | citrate | inflammation, tumors | 300 | |||||||||||||||||||||||||||||||||||||||||
18 F | FDG, FLT, FMISO, ... | 2.5 . 10 -2 | tumors | 750 |
Tab.5.7.3. Diagnostic reference levels of recommended applied activity for the most frequent examination of scintigraphic diagnostics and dose conversion factors h for used radiopharmaceuticals ... |
Note: There is a
significant difference between X-ray diagnostics and
nuclear medicinein the laws of radiation exposure. During
X-ray examination, the source of ionizing radiation is a device
and the radiation dose depends, among other things, on the number
of images performed or on the extent of the area scanned during
CT. In scintigraphy, the source of radiation is not a diagnostic
device, but the patient himself, resp. its investigating body.
Thus, we can take any number of scintigraphic images without
changing the radiation exposure of the patient. The radiation
exposure of the patient is determined here
already during the application of the radiopharmaceutical-
its type (radionuclide and chemical form) and the applied
activity.
A certain way to reduce the
radiation exposurepatient after administration of the
radiopharmaceutical, is to influence their biokinetiky -
increased hydration with a recommendation for frequent urination (or. diuretic) for accelerated
elimination of radioactive substances from the body or the
application of suitable preparations, restrictive binding
radiopharmaceutical to a particular organ (kalium
iodine KI Protection of thyroid glands when administering 131 I or 99m Tc- labeled
radiopharmaceuticals ) .
Typical
values of radiation exposure of patients from radiation
diagnostics
The average radiation exposure for the most common methods of
X-ray diagnostics (left) and radioisotope diagnostics in
nuclear medicine (right) is given in the following table
5.7.4 (based on IAEA materials)
. These are
approximate average values, provided that the guideline values
??of energy, intensity and exposure time for X-ray diagnostics
and guideline values ??of applied radioactivity for nuclear
medicine methods are observed (here these
methods are mostly radiopharmaceuticals labeled 99m
Tc, only the last line positron emission tomography of PET cancer
corresponds to 18 F-FDG) :
X-ray diagnostics | Radioisotope diagnostics | ||||||||||||||||||||||||||||||||||||
|
|
Tab.5.7.4. Approximate radiation exposure for the most common methods of X-ray and radioisotope diagnostics |
Standard typical values
of effective radiation doses in X-ray and radioisotope
diagnostics are arranged according to size in the bar graph in
Fig.5.7.1. The very lowest radiation doses (almost negligible) are in dental
X-rays (0.008 mSv for intraoral
X-rays and 0.015 mSv for OPG) . Similarly, very
low doses
are in bone orthopedic images of
the limbs
and X- rays of the lungs (approximately 0.05-0.07 mSv) . These low effective doses are caused by
two circumstances:
1. To obtain sufficiently high-quality
images, a relatively low exposure (approximately
20mAs) is sufficient ,
leading to an absorbed dose of fractions of mGy ;
2. There
are no highly radiosensitive tissues and organs in the scanned
areas (with a high tissue factor w T ) , but only relatively
radioresistant tissues with w T <0.1 .
Significantly higher radiation doses are in CT examinations , where the X-ray rotates around the
examined area and continuously illuminates it ; however,
the higher radiation dose is balanced
here by a
much more detailed diagnostic image. The radiation dose depends
on the size of the scanned area (for CT
head approx. 2mSv, CT of the abdomen up to 10mSv) . And the very highest doses , up to tens of mSv, arise in complicated
cases interventional
X-ray- guided procedures (the
last column on the left in the diagram - here the doses are also
considerably variable, depending on the complexity of the
procedure and how easily or difficultly it is
"successful" for the given patient to perform this
procedure ...) .
All these values of diagnostic radiation
doses fall into the area of very low doses
according to Fig. 5.2.3 on the left, where stochastic effects are
not only very small, but also hypothetical (as discussed above in the section " Problems of very low doses - are harmful or
beneficial ? ") ..? ..
Note to
the table and diagram: Specific values of radiation
doses are in practice highly variable , approx.
+ - 50%. The table and
diagram are averaged rounded values, more or less indicative (therefore the numerical values ??of effective doses may
not exactly match) , depending on the
devices used and the setting of their parameters, or the values
??of the applied activity of radiopharmaceuticals. Some
workplaces emphasize lower exposures and "save"
radiopharmaceuticals (adjust the quality of
images by secondary filtration during evaluation) , other workplaces use higher exposures and apply more
activity of radiopharmaceuticals (for
better primary images or shorter examination times) ... Due to the technical development of instrument
electronics and computer evaluation procedures, radiation doses
are gradually reduced .
Fig.5.7.1 Diagram of approximate typical values of radiation
doses of patients in the most common X-rays and scintigraphic
diagnostic examinations. The blue bars represent X-ray
diagnostics, the red radionuclide scintigraphic diagnostics in
nuclear medicine.
In radiation therapy
, the doses in the target tissues are, of course, quite high
- tens of Gy, cancer-cancerous tumor dose
, but also in the surrounding healthy tissues can reach units of
Gy - tolerance dose . However, even here, with proper
planning, optimization and strategy, the health benefit
is unquestionable (it is discussed
in more detail in §3.6 " Radiotherapy
", section " Physical
and radiobiological factors of radiotherapy ") .
In therapeutic
applications of radionuclides a precisely determined amount of
radioactivity is applied - it is determined either according to
verified empirical formulas, or as a lump sum according to the
given diagnosis and the required therapeutic effect (for more details §3.6
"Radiotherapy", passage " Radioisotope therapy ") . The activity of each radioactive substance
administered to a patient (especially
therapeutic applications) must be measured on a properly calibrated and metrologically verified activity
meter. The value of the applied activity is recorded
in the documentation on diagnosis or therapy ;
it is an important
data for assessing the effect of therapy and radiation exposure.
......................
Radiation risk of
stochastic effects - distribution of radiopharmaceuticals
according to radiation risk. Assessment of the acceptability of
radiation risk in the context of other occupational and
environmental risks.
Application of radiopharmaceuticals to children - choice
of activity, radiation exposure in children compared to adults.
Application of radiopharmaceuticals to women of
childbearing potential and pregnancy . ....fill in?
In pregnant women , radiation-related
radiodiagnostic procedures should be performed only when
absolutely necessary, choosing the most gentle methods possible with regard to fetal protection
. .......... fill in?
5.8.
Organizational and legislative provision of radiation protection
Everyone who uses sources of ionizing radiation is obliged,
within the limits of his competence, to take all necessary
measures to protect the health of himself, his
co-workers and other persons.
The basic legislative
framework for working with ionizing radiation is currently the
so-called " Atomic Act " on the
peaceful use of nuclear energy and ionizing radiation
(original Act No. 18/1997, the latest amendment is No. 263/2016
Sb.) And related
standards and regulations. It is primarily the SÚJB Decree No.
184/1997 - the last amendment by the SÚJB Decree No. 422/2016,
then the SÚJB Decrees No. 146/1997 and the SÚJB No. 214/1997.
The Atomic Act sets out the most general rules for working with
sources of ionizing radiation, especially important are the
objectives of radiation protection - exclusion of deterministic
effects and reduction of stochastic effects to a minimum,
principles of work with IR - justification of activities (risk
versus profit), optimization (human exposure versus costs of its
reduction), limitation (natural resources, medical exposures
...).
Central institutes
and offices for radiation protection are being set up to
supervise and coordinate the whole set of measures for the safe
use of ionizing radiation sources. The State Office of Nuclear
Safety ( SÚJB ) was established in our country . In
addition to legislative activities, SÚJB assesses projects of
workplaces with sources of ionizing radiation, issues relevant
permits and performs inspection activities at these
workplaces.
In addition, a supervisor is established at each workplace
with ionizing radiation , which deals with radiation protection
issues on site and keeps relevant documentation. The supervisor
participates in courses and seminars organized by SÚJB and other
organizations and professional societies. At
the larger workplaces of nuclear medicine (such as KNM FNsP
Ostrava), a Technical and Physical Department ( TFÚ
) has been established, which, together with other physical and
technical issues of the workplace, also provides a radiation
protection methodology from a professional point of view. In some
large medical institutes, a central Department of Medical
Radiation Physics and Hygiene has been established , which
coordinates all issues of radiation application and radiation
protection.
A set of main principles, measures and methodology of
measuring procedures to ensure the optimal level of radiation
protection at a particular workplace are written in the so-called
workplace monitoring program (what is measured, how often
is measured, where is measured, how and what is measured,
interpretation of measurement results and their documentation).
Part of the monitoring program is the determination of reference
levels - recording, investigation, intervention.
Another related material is the Quality Assurance Program for
diagnostic and therapeutic activities of the workplace, which is
a set of control and adjustment activities to ensure the proper
functioning of devices and the required quality of
radiopharmaceuticals; this is a condition for accurate and
reliable measurement and examination results. This is related to
radiation protection through optimization between the benefits
and risks of ionizing radiation application: the more valid the
diagnostic results and the better the effects of therapy, the
more the health benefits of patients outweigh the risk of
ionizing radiation side effects - and vice versa.
The set of measures, including decontamination procedures and
control measurements in the event of radiation accidents and
other extraordinary events at the workplace, are summarized in the
Workplace Emergency Code . Also in the Operating Rules The
workplace contains a number of specific principles for correct
and safe work with sources of ionizing radiation. As organizational and legislative issues
are far removed from the professional focus of the author
(physics), it will be appropriate to refer to the details
directly on the SÚJB website: http://www.sujb.cz . For a more detailed description of
the issue of radiation protection (especially in the field of
open emitters and nuclear medicine) we can also refer to the work
of experts dealing with radiation protection, eg: Huák V
.: ............. Huák V. , Paková Z .: Radiation
protection in nuclear medicine. In: Principles and practice of
radiation protection. SÚJB, Prague 2002 ............. - add Some aspects are briefly
mentioned in the syllabus " Radiation protection ".
Author's
personal note: Unnecessary
bureaucracy in radiation protection
As mentioned above, currently the field of applications
of ionizing radiation in terms of radiation protection
is monitored, coordinated and secured as thoroughly
as perhaps no other field of human activity. This must certainly
be acknowledged very positively . However, as a
physicist working for more than 40 years in the field of nuclear
and radiation physics, I would like to make a small
critical remark:
It seems to me that this overall very
high-quality concept of radiation protection is sometimes
implemented and interpreted in recent years, perhaps
overly bureaucratically.... It is sometimes based on
insignificant details, requirements important in the areas of
high activities and radiation intensities are mechanically
transferred to small workplaces (such
as nuclear medicine) , where there are virtually
no radiation risks . The number of official
"papers" and documents and their scope have grown
enormously. They emphasize and broadly describe the tasks,
powers, signatures of irrelevant persons -
various those statutory representatives, directors, deputies and
other officials who have nothing to do with radiation activity
and often do not even know about its nature and existence ...
Experts are certainly not responsible for
this situation and workers coordinating radiation protection(perhaps with the exception of isolated cases of servile
efforts to be "more papal than the pope" and zealously
multiply irrelevant regulations ...) . This
is related to the more general trend towards a hierarchical
organization of Western society, the growth of
bureaucracy and the replacement of real law by formal
justice - the golden rule "the letter kills, the
spirit revives " is forgotten .
In the field of radiation applications, as
well as radiation protection, almost exclusively professionally
well-founded people work , well acquainted with the
principles of working with radioactivity and ionizing radiation.
These workers eruditely carry out their
professional work and implement radiation protection " as
is ", to the best of their knowledge and conscience.It
should give you more confidence, without unnecessary
"bullshit" and the enormous administrative burden ..!
..
Incidentally, a similar bureaucratic
approach are seen in regulations and requirements for
the preparation and filling of radiopharmaceuticals
for nuclear medicine (§4.8, the
"Radionuclides and radiopharmaceuticals ", note" Radiopharmaceuticals - bureaucracy ") .
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