In an experiment on outbred male ICR CD-1 mice irradiated at a wide range of doses of gamma irradiation 60Co from 7.4 to 9.4 Gy with a 30-day survival rate from 100 to 5%, the dose-effect and time-effect relationships in relation to animals’ temperature and body mass index during acute radiation sickness were studied. The latent phase of acute radiation sickness is already related to a decrease in body temperature, which is determined using a remote infrared thermometer, in presence of body weight loss. A maximum dose-dependent fall in body temperature was observed in the critical phase of acute radiation sickness, when animals die in large numbers. In the recovery phase, body temperature returned to normal with subsequent body weight gain. Body temperature of irradiated mice is considered as an important criterion for their asthenia and can be used both in theoretical and applied studies.

The proportion of splenocytes with a high level of DNA double-strand breaks was determined in mice exposed to primary and secondary radiation created by bombarding of a concrete barrier (thickness 20, 40, and 80 cm) by 650 MeV protons. The proportion of splenocytes with a high level of DNA double-strand breaks was assessed by flow cytometric analysis of γH2AX+ and TUNEL+ cells. It is shown that concrete barrier can significantly reduce primary proton radiation; the severity of negative biological effects in mice irradiated in the center of the proton beam decreased with increasing the thickness of this barrier. However, the spectrum of secondary radiation changes significantly with increasing the barrier thickness from 20 to 80 cm and the distance from central axis of the beam from 0 to 20 cm, and the proportion of the neutron component increases, which also causes negative biological effects manifesting in a significant (p<0.05) increase in the percentage of splenocytes with a high level of DNA damage in mice irradiated at a distance of 20 cm from the center of the proton beam and receiving relatively low doses (0.10-0.17 Gy).

Experiment on female ICR CD-1 mice showed that non-contact infrared thermometry can be used for short-term and medium-term prognosis of animal death during the development of acute radiation syndrome. In mice irradiated with X-rays in a dose of 7.25 Gy (LD100/30), the body temperature 1 and 5 days before death was below the normal limit (<36.4°C) in 90 and 50% cases, respectively. The decrease in body temperature closely correlated with a decrease in the mean body weight in irradiated animals (from 24 to 19 g).

Purpose: Assessing the role of various factors in the formation of radioresistance is an important branch of radiobiology. The quality of drinking water, as it turned out, can significantly affect radioresistance. Against the background of studying the antiradiation properties of various types of water, differing in mineral and isotopic composition, the problem of the influence of tap water on the course of radiation injury remained underestimated. This circumstance determined the purpose of the work: to evaluate the modifying effect of tap water on the course of acute radiation sickness after X-ray irradiation of mice at an average lethal dose. Material and methods: Female ICR (CD-1) mice were irradiated with an average lethal dose once – 6.5 Gy of X-ray irradiation. After irradiation, half of the mice received tap water as drinking water, and the other half received artificially mineralized drinking water. Results: Keeping animals on tap water significantly reduced the survival rate of mice both with a single dose (log-rank test p=0.02, χ2=5.38) compared with animals receiving artificially mineralized distilled water. In addition, in the group of mice that received tap water, an increase in the rate of death of mice and a lower preservation of the group mass of animals during the development of acute radiation injury was noted. Conclusion: Tap water, used as drinking water, increases the damaging effect of radiation when X-rays are irradiated in mice.

The interaction of the oxazine dye gallocyanine with reactive oxygen ( $$^{\centerdot }{\text{O}}_{2}^{ - },$$ Н2О2) and halogen (HOCl) species has been studied by spectrophotometry, mass spectrometry, and spectrofluorimetry. It has been shown that gallocyanine reacts with HOCl and $$^{\centerdot }{\text{O}}_{2}^{ - }$$ (but not with Н2О2) to form fluorescent products. It has been found using the inhibition assay that, both in the xanthine/xanthine oxidase system and in activated human blood neutrophils, the main contribution to the conversion of gallocyanine to a fluorophore comes from its reaction with $$^{\centerdot }{\text{O}}_{2}^{ - }{\text{.}}$$ The results obtained suggest that gallocyanine can act as a fluorogenic chemosensor and be used for estimating the activation of neutrophils and the NADPH-dependent production of superoxide anion radical by neutrophils and other blood cells, as well as for testing antioxidant drugs designed with the aim to correct diseases associated with oxidative stress.

Методами спектрофотометрии, масс-спектрометрии и спектрофлуориметрии исследовано взаимодействие красителя оксазинового ряда галлоцианина с активными формами кислорода и галогенов (HOCl).Показано, что галлоцианин реагирует с HOCl и (но не с Н 2 О 2 ) с образованием флуоресцирующих продуктов.С использованием ингибиторного анализа установлено, что как в системе ксантин/ксантиноксидаза, так и в присутствии активированных нейтрофилов крови человека основной вклад в превращение галлоцианина во флуорофор вносит его реакция с Полученные результаты позволяют заключить, что галлоцианин может выполнять роль флуорогенного хемосенсора и использоваться для оценки активации нейтрофилов, NADPH-зависимой продукции супероксидного анион-радикала нейтрофилами и другими клетками крови, а также для тестирования антиоксидантных препаратов,

Purpose: To estimate the radiation fields formed after the passage of high-energy protons through the concrete protection for subsequent radiobiological experiments on animals on this model. Material and methods: The results of the calculation of the secondary characteristics of a field of mixed radiation behind the local concrete with thickness 20, 40, and 80 cm, bombarded by a proton beam of 650 MeV at the JINR Phasotron and experimental estimation of the values of the absorbed dose phantoms of mice irradiated for protection during radiobiological experiments. The calculation was performed by the Monte Carlo method according to the MCNPX program for secondary protons, neutrons, π-mesons, and gamma rays. To verify the adequacy of calculations was performed the comparison of calculated and measured in the experiment spatial distribution of activation threshold detectors for aluminum protection, as well as a comparison of the calculated values of absorbed dose for radiation protection with the results of absorbed dose measurements with a diamond detector. Results: The calculations made it possible to obtain the characteristics of the fields of mixed secondary radiation behind local concrete shields of different thickness irradiated with protons with an energy of 650 MeV and to estimate the values of absorbed doses in the irradiation sites of mice in the radiobiological experiment. The reliability of the calculations was confirmed by experimental verification of the activation of aluminum threshold detectors behind a 20 cm thick protection, as well as direct measurements using a diamond detector. Conclusion: The calculated assessment of radiation fields formed after protons pass through the concrete protection and its comparison with the results of radiation dose measurements for the subsequent radiobiological experiment on animals on this model in the interests of designing protective structures on the Moon and other space bodies, as well as biological defenses on charged-particles accelerators.

Sphingomyelins (SMs) are a class of relevant bioactive molecules that act as key modulators of different cellular processes, such as growth arrest, exosome formation, and the inflammatory response influenced by many environmental conditions, leading to pyroptosis, a form of programmed cell death due to Caspase-1 involvement. To study liver pyroptosis and hepatic SM metabolism via both lysosomal acid SMase (aSMase) and endoplasmic reticulum/nucleus neutral SMase (nSMase) during the exposure of mice to radiation and to ascertain if this process can be modulated by protective molecules, we used an experimental design (previously used by us) to evaluate the effects of both ionizing radiation and a specific protective molecule (rMnSOD) in the brain in collaboration with the Joint Institute for Nuclear Research, Dubna (Russia). As shown by the Caspase-1 immunostaining of the liver sections, the radiation resulted in the loss of the normal cell structure alongside a progressive and dose-dependent increase of the labelling, treatment, and pretreatment with rMnSOD, which had a significant protective effect on the livers. SM metabolic analyses, performed on aSMase and nSMase gene expression, as well as protein content and activity, proved that rMnSOD was able to significantly reduce radiation-induced damage by playing both a protective role via aSMase and a preventive role via nSMase.

Abstract—Intragastric administration of radioprotector indralin (B-190 drug) to outbred SPF ICR (CD-1) mice 15 minutes before X-ray irradiation at doses of 6 Gy (LD-10/30), 6.5 Gy, and 7 Gy (LD-100/30) increases the 30-day survival of the animals and positively affects the state of the central organs of immunity and hematopoiesis, as well as the number of peripheral blood leukocytes. In addition, a positive effect on the behavioral reactions of the irradiated animals and striated muscles strength was noted. In addition to these secondary features of the indralin positive effect, a significant reduction of radiation-induced DNA damage in spleenocytes was observed using flow cytometry analysis of phosphorylated histone Н2АХ (γН2АХ) (1 h and eight days after X-ray irradiation) and DNA-comet assay (eight days after X-ray irradiation). The abovementioned methods are recommended for experiments investigating the influence of radioprotective drugs on DNA damage induction and repair in the irradiated organism, as well as for initial searching of potential radioprotectors and assessment of their effectiveness level in clinical practice and experiments.

The article contains an analysis of literature data and the author’s own results on the radiobiological effects of protons at the cellular, systemic (intercellular) and organismic levels, as applied to the practical tasks of radiation therapy of oncological diseases and the protons effects on the astronauts’ organism. It is established that the proton RBE is a variable value, depending on the LET of the particles, the amount and dose rate, the presence or absence of oxygen. Proton RBE varies depending on the object of study, the type of tissue, proton energy and particle penetration depth, as well as the method for evaluating the biological efficiency of protons. which corresponds to general radiobiology. In particular, it has been shown that the RBE of protons adopted in radiation therapy at the level of 1.1 is conditional. A firmly established and repeatedly confirmed is an increase in RBE with a decrease in proton energy and, accordingly, an increase in LET. The use of elements of the physical protection of a spacecraft during exposure to protons with an energy of 170 MeV leads to an increase in LET and RBE of protons in terms of the cellularity of the bone marrow. Pharmacological agents effective in photon irradiation are also effective when exposed to a proton beam. It has been shown that natural melanin pigment and recombinant manganese superoxide dismutase helps to preserve and accelerate the resumption of blood formation in animals irradiated by protons. The Grippol vaccine increases radioresistance during proton irradiation. Neuropeptide Semax has a positive effect on the central nervous system and the strength of the forepaws of animals irradiated with protons at Bragg’s peak.

In experiments on intact mice provided by continuous access to drinking water with reduced oxidation-reduction potential (ORP) only for 30-49 days there are revealed following signs of a modification of the vital status: a slowdown in body weight gain, a decrease in behavioral activity, a decrease in the thymus and spleen mass, signs of a change in intestinal microflora composition, in comparison with the original tap water and distilled water. Reduction of ORP was achieved by distillation of water, and also by electrochemical treatment at the "Ideal" plant. In addition, water samples were used in the experiment with the addition of antioxidants: ascorbic acid and melanin, which also reduced the ORP. At X-ray irradiation in a non-lethal dose of 1.5 Gy, 24 hours after exposure to radiation, there were no statistically significant differences in the damaging effect of radiation in animals that drank water of different quality. At the same time, with an irradiation dose of 5 Gy, an acceleration in the recovery of hematological indices and behavioral activity in the use of water with reduced ORP was noted. The intake of these water samples after irradiation contributed to a statistically significant increase in the number of endogenous hematopoiesis colonies in the spleen as compared to the use of tap water.

Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme.

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.

Aim: to investigate the effect of the vaccine "Grippol" on radioresistance with respect to proton irradiation. Material and methods. The effect of the vaccine "Grippol" the survival of the animals was studied in mice CBAxC57BI F1, which was immunized for 10 days prior to proton irradiation. Results. It is shown that proton irradiation causes the death of the animals at all doses tested: 9% at a dose of 7.0 Gy; 10% — 8.0 Gy and 33% after irradiation at a dose of 8.5 Gy, at the same time the survival rate after pre vaccination study groups was 100%. It seems appropriate to further study the impact of the vaccine "Grippol" at low doses of proton irradiation using appropriate test evaluation of hematological, im-munological, genetic, physiological and other factors. Conclusion. The vaccine "Grippol" introduction into mice before lethal proton irradiation increases survival of protected animals.

Aim: to examine the effect of individual and group housing of mice on radioresistance. Material and methods. Effects of individual and group housing of mice on immunity and blood systems were studied on ICR (CD-1) and C57BI6 male mice before and after proton irradiation. Results. Group housing of intact animals resulted in a decline in the number of nucleated cells in the femur bone marrow and thymus mass. The irradiation with proton with energy of 171 MeV at a dose of 1 Gy causes a statistically significant greater reduction of the number of nucleated cells in the femur bone marrow in group-housed mice. A trend toward greater safety of the number of leukocytes in the peripheral blood and higher proliferative activity of bone marrow cells, as well as lower level of aberrant mitoses have been noted in individually-housed mice. Reduction processes in the recovery period of radiation sickness take place at a greater rate in group-housed mice. Conclusion. Group housing of male mice causes increased sensitivity of the blood and immunity systems to the effects of radiation and at the same time accelerates processes of radiation recovery.

The results of studies of individual psychophysiological mechanisms of adaptation in life-threatening situations are presented. A neurosemantic psychodiagnostic method was used, based on analysis of EEG potentials during presentation of verbal stimuli with subthreshold durations of 30 and 50 msec. Evoked responses to each stimulus were identified and processed by cross-correlation and wavelet analysis, along with assessment using neural network algorithms and analysis of results for stimuli for each lead and presentation time. Concepts of relationships between the measures analyzed and the unconscious aspects of mental activity are described. The results of studies performed using this method in different contingents of subjects, whose activities are linked with danger to life, are presented. The changes in the functioning of the basal mechanisms of unconscious reacting can clarify approaches to improving methods for providing psychological support and treatment.