Radiation-induced “bystander effects” were studied at the inter-organismal level. The experiment used mice irradiated at a dose of 3 Gy and nonirradiated bystander mice, kept together for 90 days. An analysis of the state of the bone marrow, spleen, and thymus in the experimental animals was carried out, which included an assessment of the mass of the spleen and thymus, as well as the number of nuclear cells in the bone marrow, spleen, and thymus in mice. The results of this study indicate the presence of a “bystander effect” in the nucleated cells of the bone marrow of mice. In unirradiated animals that were kept with irradiated mice in a cage without a septum, the number of nucleated cells is reduced statistically significantly ( t = 2.58; p = 0.02) compared to the control. There is an effect of increasing the number of nucleated cells in the bone marrow in the group of irradiated mice in a cage with a septum, statistically significant by 15% more than in the gamma control group ( t = 2.36; p = 0.03), i.e., the “rescue effect.” Obviously, in all organs of the hematopoietic system—bone marrow, thymus, and spleen—there are violations associated with the factor of contact of animals. It is possible that the observed radiation-induced “nontargeted effects” are realized at the level of induced changes in the DNA.

The task of studying radiation “bystander effects” at the organism level was set in the work. Irradiated and nonirradiated mice that were kept together were used in the experiment. Mice were irradiated at a dose of 3 Gy in a research radiobiological gamma installation with the sources of 137Cs. The number of leukocytes and relative number of lymphocytes in the peripheral blood of mice were estimated 3, 7, 14, 30, 60, and 90 days after the beginning of the experiment. In nonirradiated “bystander” mice kept with irradiated mice both in the cages without a partition and with a partition, there is a possible trend towards a decrease in the number of leukocytes as compared with indices in the biocontrol. During the analysis of relative number of lymphocytes, a trend towards a decrease in the index in “bystander” mice was demonstrated both when keeping without a partition and with a partition. In nonirradiated “bystander” animals when keeping with irradiated animals in the cage with a partition, a statistically significant decrease in the relative number of lymphocytes in the peripheral blood was registered on days 3 (t = 2.13; p = 0.047), 30 (t = 2.94; p = 0.01), and 90 (t = 3.07; p = 0.01) after irradiation as well as when keeping in the same cage with irradiated mice without a partition on day 60 (t = 2.24; p = 0.038) after the beginning of the experiment. A “bystander effect” in nonirradiated animals is one of possible explanations for the detected changes. In irradiated animals that were kept in the same cage with a partition together with nonirradiated animals, a statistically significant increase in the relative number of lymphocytes was registered on days 3 (t = 2.6; p = 0.02), 14 (t = 2.61; p = 0.018), and 60 (t = 2.38; p = 0.03) (“rescue effect”). Based on data obtained in the present experiment, it is assumed that the radiation “bystander effect” can have the opposite nature; that is, nonirradiated organisms are able to reduce the radiation effects in irradiated individuals (“rescue effect”).

In an experiment to study radiation "bystander effects" (BEs) at the interorganismic (systemic) level, we use mice irradiated at a dose of 3 Gy and mice that are not irradiated, bystanders, kept together. In the irradiated animals, on the 3rd and 60th days, when kept without a partition, and on the 14th day when kept in cells with and without a partition, a statistically significant decrease in the frequency of normal chromatophilic (oxyphilic) erythrocytes (NCEs) with micronuclei is revealed when compared with the gamma control. In the nonirradiated bystander-mice, kept with the irradiated mice in a cage with a partition on the 14th day and in a cage without a partition on the 60th day, a tendency to exceed the micronucleus (MN) frequency of the erythrocytes' values in the biocontrol is revealed. Based on the data obtained in this experiment, it is assumed that the radiation BE has the opposite character; i.e., nonirradiated organisms are able to reduce the radiation effects in irradiated individuals: the "rescue effect."

This paper presents the first results of research and observations within the framework of the Integrated Project for the assessment of radiation-induced nontargeted effects. The remote bystander effect, related to nontargeted effects, is one of the least studied phenomena in terms of manifestations and mechanisms. The international laboratory practice with respect to this phenomenon commenced with demonstration of the bystander effect in fish and other aquacultures. Our studies have revealed changes similar to radiation-induced pathologies in nonirradiated mice kept for three months in contact with the irradiated species (exposed to a 3 Gy γ-ray dose). Changes in behavioral responses, a statistically significant trend for decreasing spleen weight ( r = –0.416; p = 0.048), an expanding area of alopecia ( r = –0.631; p = 0.001), and other anomalies are noted. Discussions on possible mechanisms of the phenomena refer to both A.M. Kuzin’s theory of radiotoxins (1966) and the interpretation of the hypotheses investigated by C. Mothersill (2010–2019). An assumption is made on the important role of derivatives of lipid peroxides in the formation of this effect. The results of these studies indicate the need for further investigation of the radiation-induced bystander effect by using the molecular and cellular methodological approaches.

The article presents results of study of delayed effects of occupational exposure to alpha and gamma radiation on human genome. The group of 23 former Mayak employees at the city of Ozersk was involved in the study. During their work at the enterprise for plutonium processing they had been exposed to internal and external radiation. Average internal alpha radiation dose to lungs was 0.120.024 Gy, to the bone marrow – 0.0450.0087 Gy. Average individualized ex-ternal gamma radiation doses to the bone marrow and to the lungs were 1.60.1Gy, 1.80.12 Gy, respectively. Impacts of ionizing radiation and alpha particles on frequency of micronuclear cells and the components of adaptive response were assessed. Adaptive potential of lymphocytes cor-relates with doses in internal and external radiation. Results of the analysis indicate that sponta-neous DNA damage to the lymphocytes genome is related to the level of internal rather than ex-ternal damage to irradiation, of human lungs (r=0.51; p=0.015) and the bone marrow (r=0.47; p=0.026), it depends also on the duration of wok with alpha and gamma emitters (r=0.43; p=0.046). Results of the study may be useful for estimating risk of delayed effects on health sta-tus of workers dealing with radionuclides processing.

В статье представлен обзор данных литературы (с включением в него результатов собственных исследований) по индукции адаптивного ответа (АО), его формированию, некоторым механизмам, распространенности, универсальности. Предполагается, что множественность механизмов, высокая вариабельность проявлений, отсутствие способности к АО при ряде условий делает развитие АО практически непредсказуемым. Предполагается также, что индукция АО не является столь универсальным феноменом, как это считалось ранее.

В лимфоцитах периферической крови здоровых людей и больных раком предстательной железы (РПЖ) изучали поврежденность генома (частоту клеток с микроядрами и аберрациями хромосом), концентрацию активных форм кислорода (АФК), экспрессию маркеров активации (CD69), пролиферации (Ki67) и проапоптотического антигена CD95 Т-лимфоцитов, адаптивную способность. Исследовали также влияние гормонотерапии на свойства лимфоцитов и связь изученных показателей с эффективностью лечения, которую оценивали по уровню содержания в крови простатспецифического антигена (ПСА). Было обнаружено, что поврежденность генома при РПЖ не отличается от контроля, наблюдаются снижение радиочувствительности (облучение лимфоцитов в условиях in vitro в дозе 1 Гр) и повышение концентрации АФК, но эти изменения статистически незначимы. Содержание клеток, экспрессирующих маркеры CD69 и CD95, при РПЖ не изменяется, снижается экспрессия маркера пролиферативной активности Ki67. Радиочувствительность лимфоцитов при РПЖ коррелирует с экспрессией маркера CD95: при более высокой радиочувствительности этих клеток можно предполагать предрасположенность их к апоптотической гибели. Введение гормонов, курс которых проводят перед лучевой терапией, приводит к увеличению радиочувствительности лимфоцитов при РПЖ, снижению содержания АФК. Адаптивная способность лимфоцитов крови при РПЖ возрастает статистически незначимо, на нее гормоны не влияют, но высокий оксидативный статус способствует формированию адаптивного ответа. Для прогноза лечения представляется очень важным обнаруженная нами корреляционная связь между исходной (до начала лечения) частотой клеток с МЯ и эффективностью лечения: чем меньше поврежденных клеток, тем выше эффективность лечения. Полученные результаты могут иметь значение для экспериментального обоснования и понимания возможности использования лимфоцитов крови для дополнительной диагностики РПЖ и прогноза успеха его лечения.

DNA damage level was investigated by DNA comet assay in the peripheral blood lymphocytes of prostate cancer patients (28 men) and healthy donors (26 men). It was shown that the level of DNA damage analysed by DNA comet assay in neutral pH was 1,8 higher than in healthy donors. Difference is statistically significant at P

In this paper the results of research at 5–10 and 24 years after the Chernobyl accident are summarized. These results include the investigation of genomic instability, formation of the adaptive response, genome damage, and oxidative status. The studies were performed on cells in culture, mice, children and adults who lived in the contaminated areas, and liquidators of the consequences of the Chernobyl accident. Inhibition of cell proliferative activity, late cell death, and the increase in micronucleus and giant cell frequency were observed after the exposure of cells in culture in the accident zone followed by their culturing in laboratory conditions. In the progeny of the exposed cells, the effect of enhanced radiosensitivity was detected. Thus, it can be assumed that exposure of parental cells in culture in the area of the accident induced genomic instability that resulted in the development of various abnormalities in progeny cells. At the organism level, the Chernobyl zone exposure of mice caused an increase in radiosensitivity; as well, a decrease in the endotheliocyte density in the cerebral cortex and other brain tissues was observed. In the blood lymphocytes of children stimulated by PHA, a more than two times increase in micronucleus cell frequency was detected. A reduced number of individuals with significant adaptive response was found in both the juvenile and adult groups. In all investigated populations, an increased number of individuals with enhanced radiosensitivity were observed in response to low-dose radiation exposure. At 24 years after the accident liquidators were subjected to examinations, which revealed an increased frequency of cells with micronuclei and chromosome-type aberrations in blood lymphocytes, an elevated level of DNA double strand breaks, and a reduced level of reactive oxygen species compared to those of the control group. This means that the genomic instability that was accumulated by the residents of the contaminated regions and liquidators as a result of the accident leads to damage of the genetic apparatus, an increase in radiosensitivity, and hypoxia as late consequences that all are risk factors and increase the probability of the development of tumor and non-tumor diseases. The development of the above-mentioned pathological processes may occur in the distant future.

Genome damage, namely, the frequency of cells with micronuclei (MN) and chromosome aberrations, the level of DNA double-strand breaks, and concentration of reactive oxygen species (ROS), as well as 28 immunological characteristics were studied in the blood lymphocytes of Chernobyl nuclear accident cleanup workers. The goal of the work was to examine the cytogenetic and molecular biological changes in the blood lymphocytes of exposed individuals 24 years after the accident and to find the correlations between genome damage and immunity parameters. The rate of cells with MN and the total rate of the cells with all types of chromosome aberrations did not differ from those of unexposed individuals; however, the amount of chromosome type aberrations and DNA double-strand breaks were elevated in the lymphocytes of cleanup workers, whereas the concentration of reactive oxygen species was decreased. As compared with the control population cohort, cleanup workers displayed a statistically significant increase in the percent of cytotoxic CD8+ T lymphocytes, CD16+ natural killers, CD3+CD16+CD56+ natural killer cells (NK-T cells, displaying antiviral and antitumor activities), HLA-DR+ (a marker of late lymphocyte activation), and regulatory T lymphocytes (CD4+CD25+high). The level of serum immunoglobulin (IgA) increased in a statistically significant manner. The index of immune regulation decreased along with the values of phagocytic activities of neutrophils (PAN) and macrophages (PAM). Liquidators displayed statistically significant (p < 0.05) correlations of the rate of cells with MN with the content of regulatory T lymphocytes (CD4+CD25+high) and between the reactive oxygen species concentration and the content of activated T lymphocytes. A considerably larger number of correlations was detectable at the level of sufficiently reliable trends at p < 0.10, in particular, of the rates of chromosome aberrations and DNA double-strand breaks with the contents of natural killers and regulatory T lymphocytes, as well as of the rates of the cells containing MN and DNA DSBs with PAN. This suggests that the genomic instability induced by exposure 24 years ago during the cleanup activities after the Chernobyl nuclear accident is manifested now as an increased level of genome damage and a decrease in oxidative status, which can result in the cell and humoral immunity disturbance.