BIOLOGICAL EFFECTS OF IONIZING RADIATIONS.


THE STAGES OF A RADIATION DEFECT

Under the biological effect of ionizing radiations they understand their ability to cause functional, anatomic and metabolic changes at all levels of biological organization. The biological effect of ionizing radiations is predefined by the energy which is passed by radiations over to different tissues and organs.

At the basis of the biological effect of ionizing radiations there lie:


Absorption of radiation energy by a biosubstrate;

Ionization and excitation of atoms and molecules, radiolysis of water with the formation of free radicals H+ OH- and hydrogen peroxide – H2O2


Formation of active free radicals and development of primary radiation-chemical reactions and damage of high molecular compounds.


The primary effect of radiation can be linear and non-linear. There are the excitation and ionization of molecules, tissues and organs at direct radiation influence.

Ionization and excitation of the tissue atoms and molecules exposed to rays is the primary physical process, the starting mechanism of the biological effect of ionizing radiation, that is why it is called the direct effect. Thus there is a disruption of molecular associations with the formation of free radicals with high chemical activity. They interact with surrounding intact atoms and molecules (molecules of organic materials dissolved in water: proteins, nucleoprotein, lipids, enzymes and others), as a result of which there occurs their splitting with the formation of following free radicals which interact with the molecules unexposed to rays and predetermine the indirect effect of ionizing radiation, that is changes of molecules emerge not from the got energy of ionizing radiation, but from the energy of the changed molecules (during radiation exposure a very insignificant part of molecules of the organism exposed to rays find themselves under the direct effect).



The Stages Of Radiation Defect

Physical interaction, absorption of energy, ionization and excitation of molecules. Time–10^-12 sec. Molecular - level of biological organization


Primary radiochemical reactions, formation of radicals. Changes in molecules, violation of biochemistry of cells. Time - 10^-9 – 10^-3 sec. Subcellular- level of biological organization


Damages of cells: violation of structures which provide functioning and heredity of cells. Time – seconds to minutes. Cellular - level of biological organization


Violation of morphology of cells and their death. Time – minutes to hours. Tissue, organ - level of biological organization


Damages of the whole organism: violation of functions of organs and systems; morphological changes in organs and systems; death of the organism. Time – minutes to months. The whole organism - level of biological organization.


Remote somatic effects (decrease in body resistance, reduction in lifetime, development of cancer or leukosis, dystrophic changes of tissues). Time - During one's lifetime.


Genetic consequences of radiation exposure. Time – Indefinitely long time. Population - level of biological organization


The basic biosubstance of oxidizing reactions caused by free radicals are biolipids and nucleoproteides. As a result of radiation influence the structure of tissues and cells is damaged.


Ionization of atoms and molecules leads to the change in the molecular structure, which results in violation of biochemical processes in organs and tissues and displays in disorders of tissue breathing, change in enzyme system's action, violation of protein synthesis, etc.


Ionizing radiation always has a destructive effect on a living organism. The reactions of an organism to radiation exposures are variable and determined by both the nature of radiation and condition of the organism itself.


The degree of radiation defects correlates distinctly with the partial pressure of oxygen in tissues the less is the partial pressure of oxygen, the less is the radiation defect (the so-called "oxygen effect"). In the conditions of hypoxia, the radiosensitivity of the organism can decrease in 2-3 times.



FEATURES OF THE BIOLOGICAL EFFECT OF IONIZING RADIATIONS

1. The biological effect depends upon an absorbed dose and power of a radiations dose (linear dependence) growth of the dose and its power. Pathological changes emerge at all levels of organism integration the effect increases with the molecular, cellular, organ, and in an organism as a whole.


2. The effect of radiation exposure is related to the distribution of a dose in time, that is to the speed of the energy absorption. The disintegration of the same total dose into separate fragments leads to the diminishing of a radiation defect degree. The processes of renewal begin at once after radiation exposure and are able to compensate, at least partly, the caused violations.


3. The degree and form of a radiation defect are determined by radiation energy distribution in the organism. The greater destruction is caused by the radiation exposure of the whole organism which is the general radiation exposure. The lesser changes are caused by the influence of the same dose on separate parts of the organism which is called the local radiation exposure. It is important which parts of the organism are exposed to rays. The greatest consequences are caused by the radiation exposure of the stomach, and the least - by the radiation exposure of the extremities.


4. The biological effect depends upon the type of radiation.

Consequently, all types of ionizing radiations, either themselves or indirectly, cause excitation or ionization of atoms or molecules of a biological system. However, at the radiation exposure of objects by different types of ionizing radiations in even doses there emerge quantitatively, and sometimes qualitatively, various biological effects. That is why there was introduced the concept of the relative biological efficiency (RBE) of ionizing.


5. The presence of the latent period of the radiation effect. The latent period is the interval of time which covers the period from the moment of radiation exposure to the appearance of changes which are registered clinically. The duration of this period is inversely proportional to the dose absorbed. The higher the dose, the shorter the latent period is. It is necessary to bear in mind that the latent period is a conventional, purely clinical concept, because actually the reaction of radiation exposure develops persistently.


6. Accumulation ability. If one exposes an area of the skin to a dose of 1 Gy, no visual changes will be present. If one repeats radiation exposure for few days successively, erythema will develop. If radiation exposure is given every day for 2-3 months, there comes necrosis. It takes place because small changes accumulate gradually in tissues which are caused by every radiation exposure, which eventually results in great damages.


In the formation of the biological effect a special role belongs to the function of the systems which integrate an organism- the nervous system, the endocrine system and the humoral system (which transports throughout the organism toxic products being formed in tissues as a result of radiation exposure).


Nervous receptors experience the influence of toxic products, which results the violation of nervous regulatory processes and the emergence of chain

self-accelerating reactions in an organism exposed to rays, predetermines the development of a radiation defect at subsequent stages with the typical periodicity of the pathological process development.


The following important statements are the derivatives from the aforesaid:

1. The interaction of ionizing radiation with living material takes place after the laws of physics and is accompanied by excitation and ionization of atoms and molecules and primary radiochemical processes (reactions). But this is only the primary effect of radiation.


2. Ionization of atoms and molecules is only the starting mechanism for secondary processes which further develop in a living organism after biological laws. That is why the efficiency of the biological effect of ionizing radiations is estimated from the point of view of the severity of these secondary damages.


The Effect Of Ionizing Radiations On Cells And Organisms Of Warm-Blooded Animals

As a result of radiation exposure in a cell it is possible to register a greater of most various reactions– delay of division, suppression of DNA synthesis, damage of membranes and others. The degree of expression of these reactions depends on a stage of a life cycle at which a cell radiation exposure took place.


It is known that the synthesis of DNA in a cell takes place in an interphase which is divided into 3 periods- the period of synthesis of DNA (5- period), before- (G1) and postsynthetic (G2) periods, the fourth period- mitosis (M). The duration of the mitotic cycle varies in time, being disposed as follows: M <G, <5 <G. The shortest period - mitosis - is over within 30-60 minutes.


Some radiation reactions are easily born by a cell, as a result of structures damage the loss of which is very quickly restored. The most universal is the temporal delay (suppression) of cellular division that is often named the radiation blocking of mitoses. For the majority of cells cultures the delay of division is equal to approximately 1 hour per every 1 Gy. The duration of delay time also depends on a stage of a cellular cycle in which cells are at the moment of radiation exposure. It is the longest in those cases when radiation influence is experienced by cells at the stage of DNA synthesis, and the shortest- at radiation exposure in mitosis. One should distinguish the reaction of division from a complete suppression of mitosis, which sets in after the influence of higher doses when a cell continues to live for a considerable time but completely loses the ability to divide.


Lethal Effects Of Cells. The Forms Of Cellular Death

Under cellular death or the lethal effect of radiation exposure one under- stands the loss by a cell the ability to proliferation. Survived cells are those ones which preserved the ability to unlimited reproduction, that is cloning. Thus, the question is about reproductive death of a cell. This form of radio-inactivation of cells is most widespread in nature.

Another type of reproductive death of the exposed descendants cells is the formation of the so-called giant cells which emerge as a result of the confluence of two adjacent, "'sisterly" cells. Such cells are able to divide 2-3 times after which they perish.


The principal reason for reproductive cell death is the structural interaction of DNA as the so-called chromosomal alterations or aberrations. The basic types of aberrations are: fragmentation of chromosomes, forming of chromosomal bridges, dicentrics, circular chromosomes, appearance of intra-and interchromosomal exchanges and others.

Some aberrations, for example bridges, mechanically hinder the division of cells. The exchange inside chromosomes and between them results in the even division of chromosomes, the loss of the genetic material that causes the death of a cell as a result of deficiency of metabolites, the synthesis of which was encoded by the DNA of the lost part of a chromosome.


Still another form of radiation of cells inactivation – interphase death - occurs when cells enter mitosis. At radiation exposure doses of 10 Gy death can occur "under a ray" or soon after the exudation. At a radiation exposure dose up to 10 Gy death occurs within the first hours after radiation exposure and can be registered as varied degenerative changes of cells- more frequently pyknosis or fragmentation of chromatin.


The Nature Of Cells' Radiation Death

The sensitiveness of a cell nucleus is approximately six orders higher than cytoplasm. Of all intranuclear structures, DNA is accountable for the viability of a cell. The latter takes part in forming chromosomes and the transfer of genetic information. Radiation exposure causes varied intertaction in DNA: breaks of a DNA molecule, the formation of alkali-labile associations, the loss of bases and change of their composition, changes of nucleotides sequences, fusion of DNA-DNA and DNA -protein, violations of DNA complexes with other molecules.


One distinguishes single breaks of DNA when associations between separate atomic groups are violated in one of the filaments of a double spiral molecule of DNA and double when a break takes place at once near closely located areas of two chains, that results in the disintegration of a molecule. At any break, reading information from a molecule of DNA and the spatial structure of chromatin are violated.


Single breaks do not result in breakages of a molecule of DNA, because the torn filament is firmly kept in place by hydrogen, hydrophobic and other types of interaction and the opposite filament of DNA. In addition, the structure is restored well enough by the powerful system of reparation. Single breaks themselves are not the reasons for cell destruction.


With the increase of a radiation exposure dose the probability of transition of single breaks into double ones grows as well. Rarely ionizing radiations' (gamma, X-ray, fast electrons) per 20-100 single breaks cause one double break . Densely ionizing radiations cause a much greater number of double breaks of DNA and chromosomal aberrations immediately after radiation exposure.


Alongside the formation of breaks, the structure of bases in the exposed DNA, foremost of thymine. is violated, that increases the number of genes mutations. The formation of fusions between DNA and proteins of a nucleoprotein complex is marked.


Finally, the important consequence of radiation exposure is the change of epigenomic (unconnected with the nuclear material) heredity of a cell to transmitters of which are varied cytoplasmic organelles. Thus, the functional activity of the exposed cells descendants decreases. Probably, exactly it can be one of the reasons for remote consequences of radiation exposure. However the main reason of reproductive cell death at radiation exposure is the dam. age of their genetic apparatus.



The Post-Radiation Renewal (Reparation) Of Cells

A lot of radiation damages restore. Such damages are named potential. Their fate may be related to two ways: they are repaired and then a cell survives, or realized and then a cell perishes.


After the time of realization one distinguishes prereplicative, postreplicative and replicative reparations.


Prereplicative reparation (before the stage of DNA doubling) can take place by the reunion of breaks and also with the help of exclusion of the damaged bases. In the uniting of single breaks there take part of the enzymes: ligase, endo-, exonuclease, DNA ligase, which provide the eventual act of reparation - the ligase reunion.


Postreplicative reparation is the process at which a cell keeps its viability, in spite of the presence of DNA defects.


Replicative reparation (DNA renewal in the process of its reparation) is carried out by eliminating damages in the area of ​​chain growth point, or by elongation, passing the damage.


They estimate the biological effect of radiations also after radiosensitivity (the appearance of physiological reactions after radiation exposure) and radiolethality (radiolethality: ML 50/30 causes the death of 50% animals during 30 days; ML 100/30 - causes the death of 100% exosed to rays).


A radiation defect depends on personal sensitiveness to ionizing radiation and general reactivity of an organism during radiation exposure. There are specific differences in sensitiveness in mammals. A mortal dose for a man is more than 6 Gy, for a dog - 6 Gy, for a guinea-pig -5 Gy, for a rat - 8 Gy, for d bird - 8-10 Gy, for a rabbit- 12 Gy , for the simplest (amoeba) - 1000 Gy, then bacteria - hundreds of thousands of Gy (Micrococcus radiodurens lives and reproduces itself in channels of functioning atomic reactors).

Radiosensitivity depends on age (in children it Is considerably higher than in adults and elderly persons), genetic constitution, state of health (patients are usually more radiosensitive than healthy persons), nourishment (the valuable and balanced nourishment promotes radioresistance), hormonal status (the hormonal status violation promotes radiosensitivity), gender (females are more radioresistant than males), the amount of oxygen in the atmosphere during Irradiating biological objects (the oxygen effect is an increase of radio- sensitivity at the growth or decline of the oxygen partial pressure in the atmospheric sphere), the temperature (a decrease in body temperature below normal levels accompanied by an increase of radioresistance).


In 1906 I. Bergonie and L. Tribondeau noted that the radiosensitivity of tissues is directly proportional to the proliferative activity and inversely proportional to the degree of differentiation of the cells constituting it That is why haemopoetic tissue, lymphoid tissue, the gonads, the lens of an eye and others are most sensitive. This concerns muscular tissue first of all.


Depending on radiosensitivity, 3 groups of critical organs or tissues are established:

Group 1 - the whole body, gonads and the red marrow, lymphoid tissue.

Group 2 - the thyroid, fatty tissue, the liver, the kidney, the spleen, GIT, lungs, muscles, lens of an eye and organs which do not belong to groups I and II.

Group 3 — the skin, bone tissue, hands, forearms, shins and feet.


The Mechanism Of Tumor Cells' Radiation Damage

Radiotherapy is based on the biological effect of ionizing radiations . As a result of the radio influence there is the oppression of cellular division in a tumor. The doses like 0.1 Gy cause the dissociation of normal mitotic numbers. With increase in dose still more cells lose the ability to reproduction. The number of abnormal mitoses of the tumor cells grows, and the cells which continue to reproduce themselves after some divisions perish as a result of the harmful influence of chromosomal aberration and genes mutations related to the damage of DNA. There appear endophlebitis and proliferative endarteritis in the blood vessels of the tumor.

Specialists in radiotherapy aspire to the most complete destruction of tumor elements at the least damage to surrounding healthy tissues. It becomes possible because in the whole organism at the same absorbed dose the damage of tumor tissue usually occurs quicker and is expressed to a greater degree as a result of low differentiation of tumor cells and their higher radiosensitivity (the appearance of the physiological reaction after radiation exposure) in comparison with surrounding normal cells, the nervous system activity and the presence of the antiblastic defense of healthy tissues factors.


The difference in normal and tumor cell radiosensitivity is named the therapeutic interval of radiosensitivity. The greater this interval is, the easier it is to obtain tumor destruction at saving the viability of surrounding tissues.

The radiotherapeutic interval can be extended by changing radiation exposure rhythm: a set total dose of radiation exposure is divided into separate rate parts (fractions). A tumor is exposed to rays rеpeatedly, by small (2-3 Gy), middle (5-6 Gy) or large (8-12 Gu) fractions. Another way of increasing the radiotherapeutic interval is dose protraction. In these cases, each fractionated radiation exposure is prolonged by decreasing the power of a file. Radiomodifiers -radiosensitizers and radioprotectors-are also used.


Expansion of the radiotherapeutic interval is promoted by: radiosensibilizators (increase tumors radiosensitivity); B satiating a tumor with oxygen (radiation exposure in the conditions of oxygenotherapy); synchronization of cell division cycles; hyperthermia and magnetotherapy. Some chemical means strengthen a radiation defect (the primary damage of DNA) -fluorouracil, methotrexate, heparin; weaken the postradiation renewal of tumor cells-the antibiotics of the actinomycin group-actinomyicin D, aurentine and others; worsen tumors trophic conditions- gexamine and others.


Radioprotectors- reduce the sensitivity of normal tissues to radiation exposure. These are pharmaceutical preparations (serotonin, cystamine, cysteine ​​and others) hypothermia and hypoxia (inhalation of a mixture of nitro- gen with oxygen containing up to 12% of oxygen, putting a tourniquet on an extremity).


With the purpose of strengthening the radiation damage of cells, the so called radiosensibilizators are used. Here belong chemical remedies which strengthen the primary radiation defect by the increase of satiation of tumor cells with oxygen (heparin), which strengthens the primary damage of DNA. They also strengthen the radiation defect (fluorouracil, methotrexate), loosen the postradiation renewal of tumor cells (the antibiotics of the actinomycin group -actinomycin D, aurentine and others), worsen the conditions of tumor trophic (mexamine and others).


In 1938 B. Ye. Peterson on the basis of the study of radiosensitivity tumors, developed the classification of radiosensitivity which in our days is acknowledged by many scientists:

1) radiosensitive tumors - seminoma, thymoma, lymphosarcoma, Ewing's tumor, basalioma and others;

2) moderately radiosensitive - epithelial carcinoma;

3) moderately radioresistant- adenocarcinoma;

4) radioresistant tumors-neurofibrosarcona, fibrosarcomas, teratomas, skin melanomas, chondrosarcomas and others.


The radiosensitivity of tumors depends on their histological structure, the degree of differentiation of cellular elements, the correlation of stroma and parenchyma (tumors rich in stroma are less sensitive to radiation as a result of poor oxygenation), blood supply, localization, the size of a tutor (tiny tumors are more sensitive than large ones), the speed and character of growth: endophytic carcinomas are more sensitive than exophytic ones.

Success of radiotherapy of malignant tumors depends on a method of radiation exposure and a dose. There is an optimal dose within 60 to 120 Gy depending on the histological structure, localization of a tumor and other factors.

Very high doses can affect healthy tissues sound a tumor, violate vascularization, which causes tumor tissues anoxia and increases their radioresistance. Consequently, very high doses can be harmful, and small ones are simply not effective. That is why the choice of an optimal effective dose depends on the morphological structure of a tumor, a stage of disease, the state of surrounding normal tissues, the general condition of a patient and the other factors listed above.


Principles Of The Defense From The Ionizing Radiation Effect

1. The defense by amount- the diminishing of the sources power up to minimal values ​​at a workplace. The dose and activity are in inversely proportional dependence (the less the activity of radiation exposure source, the less the dose of radiation exposure is).

2. The defense by time - the reduction of the time of the contact with a radiant. The time and dose are in inversely proportional dependence (the less the time of the contact with a source of radiation exposure, the less a dose of radiation exposure is).

3. The defense by distance - the increase of the distance between a man and a radiant. The distance and dose are in inversely proportion. al dependence (the greater the distance from the source of radiation exposure, the less the dose of radiation exposure is).

4. The defense by a screen -Screening sources with materials which absorb ionizing radiations.


Protective Means Against Ionizing Radiation Effect

1. Personal: clothes, special footwear, protective means for respiratory organs, insulating suits, additional protective devices.

2. Collective: walls, pressurized production equipment, ventilation and others.


Radioactive Wastes

Radioactive wastes (RAW) are material objects and substances whose radioactive contamination exceeds the levels set by valid norms under the condition that the use of these objects and substances is not supposed.

Depending on their physical state RAW are divided into solid, liquid and gaseous.

The collection of RAW is carried out in the establishments where their formation took place. Solid and liquid RAW are kept in special containers-collectors. The uncontrolled pouring liquid RAW out into the domestic sewage system and into the environment is forbidden. Pouring liquid RAW out into the domes- tic sewage system at the simultaneous observation of the BSRU-2001 requirements is accepted. If the contents of some radionuclides in wastes exceeds the concentration possible for pouring out into the sewage system, they are collected in special containers and transported, as well as solid RAW, by a specially equipped transport to specialized organizations for processing and burying RAW.

The Deactivation Of Radioactive Wastes