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.

[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.

[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.

[Modification of the cytogenetic effects of irradiation by water with the reduced content of deuterium and heavy isotopes of oxygen].

The influence of light water with the reduced content of heavy stable isotopes of oxygen and hydrogen (deuterium) on the cytogenetic status of irradiated animals was investigated. In mice, hybrids of the first generation (CBA x C57B1) F1, the increase in the output (two-fold at the dose of 2 Gy) of aberrant mitoses in the cells of bone marrow and the decrease in the duration of the mitotic index of the first cellular cycle occurred under the influence of the two week maintenance before the irradiation on light water with ppm 35 obtained by the method of rectification as compared with the irradiated animals that were kept on the distilled water. It has been discovered that 24 h after irradiation the number of leukocytes in the group which consumed light water is lower than that in the animals that were contained on the distilled water. Moreover, the cellularity of the bone marrow in the group which consumed light water was higher than that in the animals that were contained on distilled water. The prolonged application of light water before irradiation (for 14 days) led to an increase in the sensitivity of the chromosomal apparatus of mice to γ-irradiation against the background of an increase in the mitotic activity of cells.

[Mitigation of mice radiation damage after acute and prolonged γ-irradiation by a laser device].

Effects of 7 Gy 60Co γ-radiation (acute and prolonged exposure), and combined exposure to 650 nm laser and γ-radiation on survival, peripheral blood, karyocyte count and mitotic index of bone marrow cells were studied in young C57BL/6 mice. All mice died following acute γ-irradiation at the dose rate of 1.14 Gy/min for 5 days or combined exposure for 11 days. Thirty percent survival from prolonged exposure to the dose rate of 0.027 Gy/min was observed after 19-day γ- and 38-day combined irradiation. Peripheral blood parameters did not differ significantly after acute and prolonged exposure; however, hyperchromemia was observed in mice after 24 hours of acute γ-irradiation. The count of mitoses per 1000 nucleus-containing BM cells evidenced that BM was virtually collapsed after 72 hours since the acute γ-exposure. It was demonstrated that laser can manage protection from a broad range of ionizing radiation doses and mitigate the adverse effects of equally acute and prolonged radiation exposure.

[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.

[Light-isotope water as a therapeutic agent for acute radiation disease].

Eighty outbred CD-I male and female mice (initial body mass of 31-34 g) and 40 male Wistar rats (initial body mass of 280-360 g) were randomly distributed into the experimental and control groups by sex and body mass. According to the results of experiments, consumption of rectified light-isotope water over 30 days immediately after irradiation by gamma-quanta 60Co at 5 Gy and 6.5 Gy can increase survivability rate significantly, accelerate hemopoiesis recovery and prevent body mass loss in irradiated animals. Therefore, light-isotope water can be considered as an effective agent for treatment of the bone marrow syndrome.

[Dynamics of chromosomal aberrations in primates subject to continuous and fractionated gamma-irradiation by equally effective residual doses].

The paper deals with a comparative study of two regimens of Macaca mulatta continuous 2-week gamma- and double fractionated acute irradiation by the total absorbed doses of 250 and 132 cGy, respectively; data about chromosomal aberration rates in peripheral lymphocytes were correlated. Based on calculations it was hypothesized that, regardless of regimen, by day-12 of irradiation the effective residual dose would be same, i.e. approximately 100 cGy. Analysis of instable aberration chromosomes showed similarity of the effect of gamma-irradiation by 137Cs at earlier time points (on days 2-21). In primates with the gamma-irradiation profile close to chronic (Gamma 25) the total rate of chromosomal aberrations and rate of radiation markers remain high, whereas animals exposed to fractionated radiation (Gamma 66) displayed a statistically significant (p < 0.05) reduction in cytogenetic parameters on days 36, 50 and 85. Cytogenetic analysis of peripheral lymphocytes permits the conclusion that though markedly different in dose values and rates, both regimens produce an essentially equal early damaging effect.

[Modification of radiation damage to biological objects by lasers].

A series of experiments had the purpose to study effects of gamma-rays 60Co (5 Gy) and the combined effects of laser 650 nm (1 mJ/cm2) and gamma-rays 60Co (5 Gy) on survivability, body mass, integument and mitotic index of marrow cells (MC) of young mice C57BL/6. Laser was applied to the mouse hairy back only. Ten months of gamma-irradiation brought death to 50% of mice; the combined irradiation killed only 30%. Starting on month six after gamma-irradiation, body mass was less in comparison with mice exposed to the combined irradiation. In addition, all mice lost body mass sharply before death. All gamma-irradiated mice were touched with grey over the period of 30 days; in 40 days, 10 of 20 mice had incipient local radiation alopecia on the back that passed fully within next month. However, all mice developed radiation ulcers on the fourth month since irradiation. Two mice formed also neck tumors. In 5 months tails fell off in 2 mice. Some grey streaks appeared on mice exposed to the combined irradiation 3 months later only; three mice remained black throughout the follow-up. Alopecia was found in three survivors in 5 months after irradiation. Mitotic activity of marrow cells obtained from mice on day 15 since exposure to lasing and combined irradiation was higher in comparison with cells from intact mice. In a year, the MC mitotic index was higher in mice exposed to the combined irradiation as compared with the gamma-irradiated mice.

[Cytological and cytogenetic studies of cells of Mongolian gerbils' retinal epithelium and marrow following 12-day space flight].

The paper report the results of studying mitotic activity and cytogenetic disorders in marrow and retinal epithelium cells of Mongolian gerbils in 21 - 23 hrs. of landing space apparatus Foton-M3, and the animals of synchronous and vivarium controls. Cells of the space flown gerbils displayed a statistically significant (p < 0.05) gain in the ratio of mitosis prophases and metaphases to the sum of ana- and telophases (1.7 +/- 0.3 and 2 +/- 0.1, respectively) as compared to these parameters in the synchronous and vivarium controls, where the ratio made up 0.6 +/- 0.1 and 0.7 +/- 0.1, respectively. Frequency of aberrant mytoses in the form of bridges was increased equally in both types of cells. Patterns of chromosome damages occurred in flight infer that the major portion of changes was not due to chromosome breakage but adhesion and ensuing wrong disjunction. These results seem to have been caused by acute g-stress to organism during re-entry and return from micro-g to the normal gravity.

[Comparative study of aging, UV treatment, and radiation on cataract formation].

Four randomized groups of male mice F1 (C57Black/CBA) were investigated: a) UV-irraidated (UV-A, 15 min daily during 9 months, dose 5.6 + 1.2 W/m2), b) gamma-rays irradiated (2 Gy), single, c) influence for combination of UV- and gamma-rays treatment, d) aging. The lens opacities were measured on 7th and 10th month. The expert method based on six grade scale was used for cataract measure. On 7th month the median of lens opacities were Aging group = 0; UV-irradiated group = 2.5; gamma-irradiated group = 4.75; gamma- and UV-irradiated group = 6.0. The difference between all groups was significant (p < 0.004, Kruskall-Wallis ANOVA test). The Conover post hock test has shown the significant difference for all comparison pairs (p < 0.002) with the exception of UV-irradiated group, gamma-irradiated group, gamma- and UV-irradiated group. On 10th month the lens opacities were strongly increased: Aging group = 2.5; UV-irradiated group = 5.0; gamma-irradiated group = 6.5; gamma- and UV-irradiated group = 7.5 (median). The difference between groups was significant (p < 0.0001, Kruskall-Wallis ANOVA test). The Conover post hock test has shown the significant difference for all comparison pairs (p <0.003) with the exception ofthe UV-irradiated group and gamma-irradiated group. The formation of the specific lens opacities for any group was not found. Morphology and protein composition have been investigated on 10th month. The results of morphological changes study show destructive and degenerative impairments of capsule, epithelium cells and lens fibers. However, no specific changes related to some particular actions have been found. In addition, there were no specific changes of protein composition of both water-soluble and water-insoluble fractions estimated with Differential Gel Electrophoresis technique. Obtained data mean that aging, UV-treatment, and gamma-radiation causes the similar changes of lens. It was supposed that UV-treatment or/and gamma-radiation act as an aging factor on the lens.

[Cytological and cytogenetic damages of spermatogonial cells in mice in the acute and late periods after irradiation by protons, helium ions, and gamma-rays].

Experiments with small test animals have been carried out to study the survival rate of spermatogenic cells in the acute period after exposure to protons with the energy 9 GeV, helium ions with the energy 4 GeV/nucleon, and 60Co gamma radiation in doses of 0.5-7.5 Gy and the reciprocal translocation frequency in spermatocytes under meiosis at the diakinesis-metaphase-1 stage six months after the exposure of the animals to protons with the energy 50 MeV and 9 GeV, helium ions with the energy 4 GeV/nucleon, and 60Co gamma-radiation in doses of 0.5-4.0 Gy. It is shown that the dependence of the effect on the dose is linear or near to linear for all kinds of radiation used. Relative biological effectiveness coefficients of the accelerated nuclei obtained by correlating equally effective doses of the standard and investigated radiations turned out to be higher in survival rate of type B spermatogonium and amounted to 2.0 and 1.3 for 9 GeV protons and helium ions respectively. At the same time, the use of the nonparametric method to determine the RBE coefficients in the course of finding out the reciprocal translocation frequency in spermatocytes points to an increase in the RBE coefficients of charged particles from 1.0 to 2.0.

[The "light" water effect on lenticular opacity development in mice after repeated low dose gamma-irradiation].

Action of "light" water with reduced quantities of heavy stable hydrogen and 18O ions on incidence and progress of lenticular opacity was studied in gamma-irradiated mice (60Co, 1.0 Gy). The animals were subjected to electroophthalmoscopy regularly till end of life time. The observation showed that chronic intake of "light" water safeguarded the irradiated mice against lenticular opacity. The experimental data indicate that "light" water strengthens the general body resistance as well as slows down aging of mammals.

[Cytogenetic effects in human blood lymphocytes in vitro after irradiation by protons with 1-GEV energy].

Cytogenetic disorders in peripheral blood lymphocytes of humans were studied in culture following single irradiation by protons with energy of 1 GeV. Doses ranged from 0.05 to 2.0 Gy. A large number of structural damages were observed. Nature of dependence of frequency of such irradiation markers as dicentrics and centric ring was established. Relative biological coefficient of relative energy protons was calculated as 1.2.

[Experimental studies of the relative biological effectiveness of accelerated charged particles varying in energy].

Experimental results and literary data were analyzed for the relative biological effectiveness of heavy charged particles in a broad range of energy and LET to cells of humans and other mammals in culture, whole body of laboratory animals, microorganisms, bacteriophages, and plants. Analyzed were data obtained with the use of a diversity of tests of acute and delayed lesions induced by ionizing radiation, cancers and cataracts, specifically. Non-parametric methods are applied in parallel to the classic method of calculating the coefficients of relative biological effectiveness by correlating the equal-effective doses of the standard and a given radiation. Consideration is given to factors that may modify RBE values estimated for different types of radiation.

[The influence of the water with decreased content of heavy stable hydrogen and oxygen (18O) isotope on development of radiation injuries at gamma-radiation in low dose].

The investigations of the water with decreased content of heavy stable hydrogen and of oxygen (18O) isotope received by the method of rectification were conducted on development of radiation injuries in organisms of the experimental animals. The objects of the investigation were male mice of Balb/c line. The animals were irradiated at the unit PX-gamma-30 with the gamma-radiation source 60Co in the dose of 25 sGy. It was observed that the water with decreased content of heavy stable hydrogen and of oxygen (18O) isotope influences positively the processes of restoration. It was manifested in decrease of the degree of gravity of radiation injuries in immune system organs (thymus and spleen), peripheral blood and marrow cells.

[Morphological and cytogenetic disorders in rats following chronic exposure to elevated radiation]. / Morfologicheskie i tsitogeneticheskie narusheniia u krys, nakhodivshikhsia v usloviiakh povyshennogo radiatsionnogo fona na protiazhenii dlitel'nogo vremeni.

Object of the investigation were effects of elevated radiation background on specific body systems in two generations of rats that had been chronically exposed to radiation in the most badly polluted areas of the Kaluga district and eaten local food. Findings included some compensatory deviations in the white blood count, decrease in karyocytes and increase in chromosomal aberration rate in nucleus-containing cells from the femoral bone marrow in younger animals of several groups, morphologic and histochemical shifts in mucous membrane of the esophagus and the stomach, and morphofunctional changes in neurons and glia of the cerebral cortex. These changes are compensatory-adaptive by nature and indicative of destabilization of homeostasis in experimental animals.

[Combined effect of immobilization stress and gamma-irradiation on the blood-forming system in mice]. / Sochetannoe vliianie immobilizatsionnogo stressa i gamma-izlucheniia na krovetvornuiu sistemu myshei.

Experiments with mice BALB/C were aimed at studying effects of immobilization stress and consecutive total gamma-irradiation at the dose of 2.0 Gy. Disorders in the blood system were shown to be a function of phase of the general adaptation syndrome (GAS). Acute gamma-irradiation on the stage of GAS resistance inhibited adaptive and compensatory potentials of the blood-forming system, whereas chronic stress by itself increased the spontaneous rate of chromosomal aberrations in nucleus-containing bone marrow cells in experimental animals.

[Probability of lens opacity and mature cataracts due to irradiation at various LET values]. / Veroiatnost' razvitiia pomutneniia khrustalika i obrazovanie zrelykh katarakt pri deistvii izluchenii s razlichnymi znacheniiami LPE.

The paper reviews experimental and clinical data on the incidence of opacity of the lens and cataract development in animals and humans due to exposure to different types of radiation. Cataractogenous effectiveness of fast neutrons, accelerated ions of carbon, helium, neon and argon with the energy of 300 MeV/nucleon, and 137Cs gamma-radiation was compared. Analysis of the incidence of opacity of the lens in consequence of low doses gave high RBE estimates (from 10 to 40). The extremely high cataractogenous effectiveness of accelerated ions makes on thing that the existent space radiation limits, particularly in part of the GCR effects on the lens and permissible doses for cosmonauts, should be reconsidered towards mitigation. The authors discuss issues of threshold radiation doses that do not markedly increase incidence and rate of the lens opacity development in the post-exposure period.