[CYTOGENETIC EFFECTS IN MICE BONE MARROW AFTER IRRADIATION BY FAST NEUTRONS].

Mechanisms of damaging mice bone marrow cells by 1.5 MeV neutrons at the dose of 25-250 cGy, dose rate of 23.9 cGy/s and γ-quants 6°Co as a standard radiation were studied. The mitotic index and aberrant mitoses in marrow preparations were counted in 24 and 72 hours after irradiation. Coefficients of relative biological effectiveness (RBE) of fast neutrons 24 and 72 hours post irradiation calculated from mitotic index reduction and aberrant mitoses formation were within the range from 4.1 ± 0.1 to 7.3 ± 0.1. Mean time of the existence of chromosomal aberrations in marrow cells was determined. For the specified doses from γ-rays, the period of aberrations existence was 1.4-1.1 cycles and for neutrons, 1.0-0.6 cycles. Morphologic analysis of neutron-induced damages and ratio of the most common breaks demonstrated a high production of bridges, which outnumbered cells with fragments in 3 to 4 times suggesting a more destructive effect on the genetic structures of cells. RBE of fast neutrons is a variable that grows with a radiation dose. Moreover, RBE estimated after 72 hours exceeded values it had 24 hours after irradiation.

Early Response of Mouse Bone Mrrow Cells to Short-Term Irradiation in a Wide Range of Doses.

Experiments on mice irradiated with γ-rays in a wide range of doses, from 0.5 to 400 cGy and the bone marrow have shown cytogenetic and cytological effects ranging from I cGy dose 24 hours after exposure to radiation. Dose-independent reduction of the number of nucleated cells in the bone marrow, normal or even elevated levels of mitotic activity, and extreme dependence of the type of chromosomal aberrations on the radiation dose with the maximum in the region of 7.5 cGy were observed in the dose range from 1 to 20 cGy. A linear dose-dependent decrease of the cell.number in the bone marrow, a decreased mitotic activity and increased number of aberrant mitosis were marked in the dose range from 20 to 400 cGy. The findings are discussed in terms of their application for explaining the mechanisms of hormesis, adaptive response, as well as the appropriateness of accounting the parameters studied for solving problems of regulation of permissible doses.

[DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE].

The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/µm to 1.6 keV/µm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect.

[IMMEDIATE RADIOBIOLOGICAL EFFECTS IN MICE FOLLOWING γ-IRRADIATION BY LOW DOSES].

Outbred CD-1 mice females aged 4 to 4.5-months were investigated in 21-22 hours following total γ-irradiation at 10, 25, 50, 75, 100 and 200 mGy. Loss in bone marrow karyocytes, as well as spleen and thymus mass reductions were significant in the group of animals irradiated at 50 and 200 mGy and less dramatic in mice irradiated at 75 mGy. The orientative-trying behavior reaction (OTBR) in the open field tested in 19-20 hours after exposure to 10 and 25 mGy was reliably stronger than in the group of biological control; however, emotional status (ES) in the animals that received 10 mGy dropped significantly. Mice irradiated at 50 mGy were found to weaken the grip of their front limbs. Dose levels differing in opposite radiobiological effects on the parameters under study were established. Doses in the range from 10 to 25 mGy maximized OTBR and ES, while doses of 50, 100 and 200 mGy produced high reactions of the immune and hemopoietic organs.

[CYSTEAMINE-INDUCED MODIFICATION OF CYTOGENETIC DAMAGES TO THE CORNEAL EPITHELIUM OF MICE EXPOSED TO CORPUSCULAR RADIATION WITH VARYING LINEAR TRANSFER ENERGIES].

Cytogenetic damages to cells of the corneal epithelium were studied in mice exposed to protons (10, 25, 50 and 645 MeV), ions of boron, carbon and neon, and X-rays (180 keV) within the dose range from 25 to 750 cGy and injected with a radioprotector. Animals were subjected to a single exposure. The protective effect of ß-mercaptoethylamine was tested in the experiment. The radioprotector (0.2 ml) was introduced intraperitoneally 30 minutes before exposure in 350 mI/kg dose. Control animals received the same amount of sodium chloride solution. The animals were sacrificed by cervical dislocation in 24 and 72 hrs. after exposure. It was shown that cysteamine effectively protects in vivo corneal epithelium cells of mice exposed to electromagnetic radiation or protons in a broad energy spectrum (10 to 645 MeV), and to a broad range of radiation doses (25 to 750 cGy), as judged from levels of aberrant mitosis and mitotic activity. The radioprotector exhibited the highest effectiveness in animals exposed to the doses of 50 to 300 cGy. These findings prove that cysteamine may potentially be used for pharmacological protection from protons. The radioprotector failed to prevent chromosomal aberrations after exposure to heavy charged particles of boron, carbon and neon, which implies the need to design radioprotectors against this type of corpuscular radiation specifically.

[Cytogenetic damage to the corneal epithelium of mice due to the in vivo exposure to ionizing radiation with different levels of linear energy transfer].

Damages to corneal epithelium cells were studied in mice irradiated by protons with the energies of 10, 25, 50 and 645 MeV, 60Co γ-quanta and accelerated ions of boron, carbon and neon with the energies of 7.5; 2.5 and 6.0 MeV/nucleon, respectively. X-rays (180 keV) were used as a standard radiation. Animals were exposed to a single dose in the range from 25 to 760 cGy. The mitotic index and aberrant mitoses were counted in corneal preparations in 24 hrs after irradiation. No matter the type of radiation, the mitotic index had an inverse dose dependence, i.e. the higher the dose, the lower the mitotic index. Exposure to all types of radiation resulted in a sharp increase in the number of chromosomal aberrations in the corneal epithelium; frequency of aberrations was a function of dose and type of radiation. The number of chromosomal aberrations displayed a peculiar direct dose dependence irrespective of type of radiation; however, heavy ions of carbon and boron are the most damaging to the cytogenetic apparatus of epithelial cells. Protons at the Bragg peak and ensuing fall, and of 50 MeV also contribute to the production of chromosomal aberrations as compared with sparsely ionizing gamma- and X-rays and high-energy protons with low linear energy transfer. Coefficients of relative biological effectiveness were calculated based on the mitotic index and evidence of aberrant mitosis.

[MODIFICATION OF THE PROTON BEAM PHYSICAL PARAMETERS AND RADIOBIOLOGICAL CHARACTERISTICS BY ELEMENTS OF SPACECRAFT RADIATION PROTECTION].

The experiment was performed with outbred ICR (CD-1). female mice (SPF). The animals were irradiated by 171 MeV protons at a dose of 20 cGy. The spacecraft radiation protection elements used in the experiment were a construction of wet hygiene wipes called a "protective blind", and a glass plate imitating an ISS window. Physical obstacles on the path of 171 MeV protons increase their linear energy transfer leading to the absorbed dose elevation and strengthening of the radiobiological effect. In the experiment, two types of obstacles together raised the absorbed dose from 20 to 23.2 cGy. Chemically different materials (glass and water in the wipes) were found to exert unequal modifying effects on physical and biological parameters of the proton-irradiated mice. There was a distinct dose-dependent reduction of bone marrow cellularity within the dose range from 20 cGy to 23.2 cGy in 24 hours after exposure. No modifying effect of the radiation protection elements on spontaneous motor activity was discovered when compared with entrance protons. The group of animals protected by the glass plate exhibited normal orientative-trying reactions and weakened grip with the forelimbs. Rationalization of physical methods of spacecrew protection should be based as on knowledge in physical dosimetry (ionizing chambers, thermoluminescent, track detectors etc.), so the radiobiological criteria established in experiments with animals.

[Radiobiological effects of total mice irradiation with Bragg's peak protons].

Outbred CD-1 female mice were irradiated in a proton beam (171 MeV, 5 Gy) on the phasotron at the Joint Institute of Nuclear Research (Dubna, Russia). Radiation was delivered in two points of the depth dose distribution: at the beam entry and on Bragg's peak. Technical requirements for studying the effects of Bragg's peak protons on organism of experimental animals were specified. It was recognized that protons with high linear energy transfer (mean LET = 1.6 keV/microm) cause a more severe damaging effect to the hemopoietic system and cytogenetic apparatus in bone marrow cells as compared with entry protons and 60Co gamma-quanta. It was shown that recovery of the main hemopoietic organs and immunity as well as elimination of chromosomal aberrations take more time following irradiation with Bragg's peak protons but not protons with the energy of 171 MeV.