Biological Effect of Ionizing Radiation

changes caused in the life activity and structure of living organisms under the influence of shortwave electromagnetic radiation (X rays and gamma rays) or fluxes of charged particles (alpha particles, beta radiation, protons) and neutrons.

Investigations of the biological effect of ionizing radiation were begun immediately after the discovery of X rays (1895) and radioactivity (1896). In 1896 the Russian physiologist I. R. Tarkhanov showed that X rays passing through living bodies disrupted their activity. Investigations of the biological effect of ionizing radiation began to develop intensively with initial use of atomic weapons (1945), and then with the peaceful use of atomic energy.

A number of general principles characterize the biological effect of ionizing radiation. (1) Profound disturbance of life activity is caused by infinitesimally small quantities of absorbed energy. Thus, the energy absorbed by the body of a mammalian animal or of a human in being irradiated with a lethal dose when converted to heat energy would raise the body temperature by only 0.001°C. An attempt to explain the “discrepancy” between the quantity of energy and the resulting effect led to formulation of the target theory, according to which radiation damage results when the energy reaches the especially radiosensitive part of the cell—the “target.’’ (2) The biological effect of ionizing radiation is not limited to the organism subjected to irradiation but may spread to succeeding generations, which is explained by the effect on the hereditary apparatus of the organism. It is precisely this characteristic which places very sharply before mankind the problem of studying the biological effect of ionizing radiation and of protecting the organism from radiation. (3) A concealed (latent) period is characteristic of the biological effect of ionizing radiation, that is, development of radiation sickness is not immediately observed. The duration of the latent period may vary from a few minutes to decades, depending on the irradiation dose and the radiosensitivity of the organism and of the observed function (Figures 1 and 3). Thus, radiation in very large doses (tens of thousands of rads) may cause “death under the ray,” while prolonged irradiation in small doses leads to changes in the nervous and other systems and to the development of tumors years after irradiation.

Figure 1. Influence of radiation dosage on the number (in percent) and survival times of bone-marrow cells in rats

Radiosensitivity of various species of organisms varies. The death of half the irradiated animals (under general irradiation) in the course of 30 days after irradiation (lethal dose—LD 50/30) is caused by the following doses of X rays: guinea pigs 250 roentgens (R), dogs 335 R, monkeys 600 R, mice 550–650 R, crucian carp (at 18°C) 1,800 R, snakes 8,000–20,000 R. Unicellular organisms are more resistant: yeasts die under a dose of 30,000 R, amoebas 100,000 R, and infusoria withstand irradiation at a dose of 300,000 R. Radiosensitivity of higher plants also varies: lily seeds completely lose their germination capacity at a dosage of 2,000 R, but cabbage seeds are not affected by a dose of 64,000 R.

Age, physiological condition, intensity of metabolic processes, and conditions of irradiation also have great significance (Figure 2). Along with these—in addition to the

Figure 2. Survival rate of irradiated mice (lethal dose, 50/30) as a function of age

irradiation dose to the organism—a role is played by the dose rate, rhythm, type of radiation (single, multiple, intermittent, chronic, external, general or partial, internal) and its physical characteristics, which determine the depth of energy penetration in the organism (X-ray and gamma radiation penetrate deeply, alpha particles up to 40 micrometers, beta particles a few mm), and the density of the ionization caused by the radiation (under the influence of alpha particles it is greater than with other types of radiation). All these characteristics of the active radiation agent determine the relative biological effectiveness of radiation. If radioactive isotopes that have entered the body serve as the source of radiation, then their chemical properties, which determine the isotope’s participation in metabolism and its concentration in one or another organ, and consequently the type of irradiation of the organism, have great significance with regard to the biological effect of the ionizing radiation which they emit.

The initial effect of any type of radiation on any biological object begins with absorption of the energy of irradiation, which is accompanied by excitation of molecules and their ionization. When there is ionization of water molecules (an indirect effect of radiation) in the presence of oxygen, active radicals (OH^- and others), hydrated electrons, and hydrogen peroxide molecules appear, which are then included in the chain of chemical reactions within the cell. When there is ionization of organic molecules (a direct effect of radiation), free radicals appear, which, being included in the chemical reactions occurring in the body, disrupt metabolism, and, causing the appearance of compounds alien to the body, disrupt the life processes. In a medium-sized cell (10^-9 g) approximately 1 million such radicals will appear with a radiation dose of 1,000 R, each of which, in the presence of oxygen from the air, may initiate chain oxidation reactions which will increase by many times the number of altered molecules in the cell and will cause subsequent changes in supramolecular (submicroscopic) structures. Clarification of the important role of free oxygen in chain reactions leading to radiation sickness, the so-called oxygen effect, has made possible the development of a number of radioprotective substances which cause artificial hypoxia in body tissues. Of great significance is energy migration along the molecules of biopolymers, as a result of which absorption of energy at any location on a macromolecule leads to affection of its active center (for instance, to inactivation of the protein enzyme). The physical and physicochemical processes that underlie the biological effect of ionizing radiation—that is, the absorption of energy and ionization of molecules—occur in fractions of seconds (Figure 3).

Subsequent biochemical processes of radiation damage

Figure 3. Diagram of the development of radiation sickness (center) and methods of affecting it (right)

develop more slowly. The active radicals formed disrupt normal enzyme processes in the cell, which leads to a decrease in energy-rich (macro-ergic) compounds. Synthesis of deoxyribonucleic acid (DNA) is especially sensitive to irradiation in cells that are dividing intensively. Thus, as a result of chain reactions initiated during absorption of radiation energy, many cell components change, including macromolecules (DNA, enzymes, and others) and relatively small molecules (adenosinetriphosphoric acid, coenzymes, and others). This leads to destruction of enzyme reactions, physiological processes, and cell structures.

The effects of ionizing radiation cause damage to cells. Most important is the disruption of cell division, or mitosis. With radiation in relatively small doses a temporary interruption of mitosis is observed. Large doses may cause complete cessation of division or destruction of the cells. Disruption of the normal course of mitosis is accompanied by chromosomal reorganization and the advent of mutation, which lead to shifts in the genetic apparatus of the cell, and consequently to changes in succeeding cell generations (cytogenetic effect). When the sex cells of multicellular organisms are irradiated, disruption of the genetic apparatus leads to changes in the hereditary characteristics of the organisms which develop from them. With irradiation in large doses, swelling and pycnosis (condensation of chromatin) of the nucleus occur, followed by the disappearance of the nuclear structure. Change in viscosity, swelling of protoplasmic structures, formation of vacuoles, and increased permeability are observed in the cytoplasm with an irradiation dosage of 10,000–20,000 R.

Comparative study of the radiosensitivity of nucleus and cytoplasm has shown that in most cases it is the nucleus that is sensitive to irradiation (for example, irradiation of the nuclei of heart muscle of a triton with a dose of several protons per nucleus caused typical destructive changes; a dose several thousand times larger did no damage to the cytoplasm). Numerous data indicate that cells are most radiosensitive during division and differentiation; growing tissues are the first to be affected by irradiation. This makes irradiation most dangerous for children and pregnant women. Radiotherapy of tumors is based on this very fact—the growing tissue of the tumor is destroyed by irradiation doses that damage surrounding normal tissues to a lesser degree.

Changes arising in irradiated cells lead to disruptions in tissues, organs, and life activities of the entire organism. Especially pronounced is the reaction of tissues in which certain cells live a relatively short time. These are the mucous membranes of the stomach and intestines, which, after irradiation, become inflamed and covered with ulcers, which leads to disturbance of digestion and absorption, then to emaciation of the body, its poisoning with the products of cell decomposition (toxemia), and the penetration of bacteria living in the intestines into the blood (bacteremia). The hematogenous system is severely damaged, which leads to a sharp decrease in the number of leukocytes in the peripheral blood and to a decline in its defensive properties. Manufacture of antibodies falls off simultaneously, which even further weakens the body’s defensive forces. (The lowering of the irradiated body’s capacity to manufacture antibodies and thus resist the implantation of foreign protein, is used in organ and tissue transplants: the patient is irradiated before the operation.) The number of red blood cells is also decreased, which causes disruption of the respiratory function of the blood. The biological effect of ionizing radiation causes disturbance of sexual function and of sex-cell production to the point of complete sterility in irradiated organisms. The nervous system plays an important role in the development of radiation sickness in animals and man. Thus, in rabbits a fatal outcome with irradiation of 1,000 R is often determined by disturbances in the central nervous system, causing cessation of heart activity and paralysis of breathing.

Research on the bioelectric potentials of the brains of irradiated animals and of persons undergoing radiation therapy have shown that the nervous system reacts to the effect of radiation earlier than other bodily systems. Irradiation of a dog with 5–20 R and chronic irradiation in 0.05-R doses lead to changes in conditioned reflexes when a total of 3 R is reached. Disturbances in the activity of the endocrine glands also play a large role in the development of radiation sickness.

Aftereffects, which can be quite prolonged, are characteristic of the biological effect of ionizing radiation, since, when irradiation is ended, the chain of biochemical and physiological reactions initiated with absorption of radiation energy continues for a long time. Blood changes (decrease in the number of leukocytes and red blood cells), nephrosclerosis, cirrhoses of the liver, changes in the muscular membrane of the blood vessels, early aging, and the appearance of tumors are all part of the long-range consequences of irradiation. These processes are connected with the disruption of metabolism and of the neuroendocrine system, and also with damage to the genetic apparatus of body cells (somatic mutations).

By comparison with animals, plants are more radioresistant. Irradiation in small doses may stimulate plant life activity (Figure 4)—sprouting of seeds, intensity of rootlet growth, accumulation of green matter, and so on. Large doses (20,000–40,000 R) cause a decline in the survival rate of plants, the appearance of deformities, mutations, and tumors. Disruption of plant growth and development with irradiation is, to a significant degree, connected with changes in metabolism and with the appearance of primary radiotoxins, which in small quantities stimulate life activity but in large ones suppress and disrupt it. Thus, washing irradiated seeds within a period of 24 hours after irradiation decreases the inhibitory effect by 50–70 percent.

Radiation damage to the organism is accompanied simultaneously by an ongoing process of recovery, which is connected with the normalization of metabolism and regeneration of cells. For this reason, fractional irradiation or irradiation of a small dose rate produces less damage than does massive action. Study of the processes of recovery is important in the search for radioprotective substances and for drugs and methods of body defense against radiation. All the inhabitants of the earth are constantly subjected, in small doses, to the effect of ionizing radiation—cosmic rays and radioactive isotopes which are part of the organisms themselves or of the surrounding environment. Tests of atomic weapons and the peaceful application of atomic energy increase radioactive background. This increases the importance of studying the biological effect of ionizing radiation and searching for protective measures.

The biological effect of ionizing radiation is used in biological research, in medicine, and in agriculture. Radiation

Figure 4. Number of sprouted potato eyes of the Lorkh variety as a function of radiation dosage

therapy, X-ray diagnosis, and radioisotope therapy are based on the biological effect of ionizing radiation.

In agriculture radiation effects are used for the purpose of developing new plant forms, for the presowing processing of seeds, for the war against pests (by means of breeding and releasing males sterilized by irradiation on affected plantations), for radiation preservation of fruits and vegetables, for protection of the products of plant growing from pests (doses destructive to insects are harmless to cereal grains), and so on.