The article is aimed to consider phenomenological aspects of the recently discovered the general biological phenomenon, caused as the “rescue effect”. It means that irradiated cells or organisms show a biopositive response as a result of feedback signals from non-irradiated cells or organisms contacted with them. The analysis of the results presented in the world literature and obtained with various experimental models using primary human fibroblasts (NHFL), normal human dermal fibroblasts (NHDF), Danio Rerio embryonic fibroblasts (ZF4), normal human lung fibroblasts (W138), human macrophage and hepatocyte cell lines (U9347 and HL-7702 respectively), as well as cells of the "immortal" HeLa lineage, human melanoma (Me45), and lung adenocarcinoma (A549) was carried out. It is shown that the induction of the "rescue effect" depends on the combination of cell lines used as irradiated targets and bystander cells. The effects obtained in the Danio Rerio embryo model of (in vivo studies) are also discussed. The mechanisms associated with the induction of the "rescue effect" and soluble signaling factors (chemical messengers) that cells/organisms receive as biological "help" in the form of feedback signals sent by non-irradiated cells/individuals are considered. The ways of implementing the two identified types of the "rescue effect" are discussed. The type of ionizing radiation used, its dose range, the spectrum of irradiated and non-irradiated cells, and the various biological endpoints are crucial in order to differentiate or combine the two phenomena into a single phenomenon. In the future, this will not only be fundamental, but also of great practical importance related to drug development, optimization of radiotherapy methods and improvement of treatment outcomes for cancer patients.

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 the study conducted on outbred female mice, the radiation-induced “bystander effect” and the “rescue effect“ were found to be formed at an inter-organismic level. Unirradiated and gamma-irradiated (3 Gy) outbred white female mice were placed in one cage. The effect of co-residing was registered with the use of hemopoietic cells of peripheral blood by comparing to the population of hemopoietic cells in irradiated and unirradiated mice placed in different cages. The “bystander effect“ was observed in the monocytes subpopulation on the 3rd, 7th and 60th days. The effect was also observed in the neutrophils subpopulation on the 7th and 90th days. The “rescue effect” was observed in irradiated cells. The 5.8-fold (increase in eosinophils was registered on the 30th day (t=2.85; p=0.01), the 1.6-fold increase in eosinophils was observed on the 60th day, the 3-fold increase in eosinophils was registered on the 90th day (t=2.28; p=0.04). The effect of neutrophils subpopulation is slightly expressed, it can be considered as a tendency to increase the number of neutrophils on the 14th and 30th days. When the “rescue effect“ on irradiated mice was estimated with the use of monocytes the 5.7-fold increase was registered on the 30th day (t=2.94; p=0.01), the 7.3-fold increase was registered on the 90th day (t=2.41; p=0.03). According to the data obtained the “bystander effect” and the “rescue effect” are observed in all studied hemopoietic cells subpopulations, however they respond differently. The findings demonstrate the manifestation of the “bystander effect” and the “rescue effect” at the inter-organismic level. However, their intensity and trend depend to a large extent on the time period after irradiation, the contact type (tactile or olfactory) and a cellular subpopulation.

Most studies of radioadaptive response (RAR) in vivo have revealed its effective induction both by chronic and single irradiation of a human organism with low doses. The classical way of the for-mation of RAR on the human peripheral blood lymphocytes (PBL) was noted as in occupationally irradiated personnel as in residents of areas with increased natural or man-made accidental high background radiation. In some studies, the liquidators of the Chernobyl accident and children liv-ing in the Chernobyl pollution zone showed the phenomenon of increasing the radiosensitivity of PBL. A comparative analysis of the influence of two types of radiation (gamma and betta) with close RBE showed comparable effectiveness to induce an adaptive response in human PBL in the mode of chronic exposure in the long term. Evidence of RAR in vivo was also obtained in the study of DNA end-points and chromosomal damage. In an experiment with the effect on neutrophils of peripheral blood of the elderly people (age 63-84 years) induced by acute gamma-rays in a wide range of doses (0.1; 0.25; 1; 4 and 10 Gy) the greatest radioresistance of their phagocytic and lysosomal activity is shown. Gamma-rays at low doses (0.1 Gy) stimulated the formation of extracellular traps by neutrophils in vitro using activated pyrogen (Pyrogernalum). The article presents some mechanisms of RAR in vivo. The study of radioadaptive response should be considered as an indispensable factor for assessing and controlling individual human radiosensitivity.

The paper summarizes results of medical examination of two groups of patients, the public members resided in high natural background radiation areas and occupationally irradiated nu-clear and health workers. Adaptive response to chronic exposure to radiation was found to last much time and, thus, its impact on the development of late health effects, including cancer, may be great. In vitro studies demonstrate that induction of adaptive response is the multistep process including the excision reparation of nucleotides, nonhomologous DNA ends joining, antioxidative system and cell cycle control factors. The review presents data on effects of low doses radiation of high or low relative radiation effectiveness(RBE). Some damaged peripheral blood lympho-cytes demonstrated increased radioresistance to high radiation doses, results of examinations of both the public members and professionals.

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.

Catabolic products of the lipoperoxidative cascade (LPC), including diene conjugates, ketodienes, and carbonyl compounds, as well as essential lipid bioantioxidants (BAO)--vitamins E and A--were determined in blood plasma of 428 children aged 0-7 years residents of areas contaminated with radionuclides after the Chernobyl Power Plant accident. Individual external gamma-irradiation doses (D) were determined. Gamma-irradiation accounted for more than 90% of total radiation loads and correlated with irradiation from absorbed sources in residents of the areas examined. Before examination, oral multivitamin therapy (with preparations containing the BAO determined in this work) was administered to a group of children (group I, n = 90) comparable to the group receiving no therapy (group II). Group II had two to six times higher mean levels of all LPC catabolic products and two to three times lower levels of vitamins E and A in comparison to age-matched subgroups of group I. In group II, individual shifts in the levels of all catabolic products achieved pathogenic stressor magnitudes at maximal regional radiation loads. Antenatal exposure and exposure over the first year of life caused the strongest pathogenic effects. BAO therapy strongly normalized the levels of LPC and vitamins (E and A) at all doses (up to 7 cSv) and increased the radiation resistance of the subjects. A total of 47 linear correlations were found at a p < 0.05 level (r = 0.4 to 0.7 for 54% and p < 0.02 for 87% of equations) between low radiation doses and the extent of deviation of all metabolites studied from their normal levels. The multiplicity of radiation dose--effect correlations found under various conditions suggest that pathological signs found in the children examined were due to irradiation. LPC system disorders developed at low doses and displayed no threshold effect. The data suggest that these disorders resulted from free-radical chain-branched LPC reactions caused by chronic exposure to low doses of strongly ionizing radiation under conditions of BAO deficiency.

Essential lipid bioantioxidants (BAO) (vitamins E and A) and catabolic products of the lipoperoxide cascade (LPC) (diene conjugates, ketodienes, and carbonyls) were determined in blood plasma of children aged 11 days to three years (n = 123) who are residents of regions contaminated with radionuclides (5-40 Ci/km2 of 137Cs) discharged during the Chernobyl power plant accident. Individual antenatal radiation loads Da of children and total radiation doses of their mothers Dm were also determined as external gamma-radiation loads, which correlate with internal radiation doses for permanent residents of contaminated regions. Before examination, therapy with multivitamins containing BAO determined in this work was administered to groups of pregnant women and their children (group I, n = 48) age-matched to a group that received no therapy (group II, n = 99). In group II, reduced concentrations of vitamins E and A decreased to levels indicating severe vitamin deficiency and displayed inverse correlations with Dm and Da. However, in group I these decreases and inverse correlation were only characteristic of initially normal levels of tocopherol. In group II, increases in Dm and Da caused stress-related increases in blood levels of diene conjugates and ketodienes (which was stronger than in group I with increases in Da) and, because of this, E and A vitamin deficiencies. In group I, LPC levels inversely correlated with Dm. We found nine significant correlations of radioloads of mothers with BAO and LPC pathologies of their children. The total pathogenic effectiveness of Dm in relation to LPC and BAO of children is comparable to the effectiveness of Da, which is the most hazardous radiation load. The possibility of existence of a radiation-induced protective response mobilizing BAO from depots into the blood stream is considered. BAO therapy increased the radiation resistance of children. A hypothesis was formulated that the uptake by children of their mother's radioactive Chernobyl isotopes in amounts adequate to their radiation loads is the mechanism of correlations of Dm with long-term pathogenic effects on BAO and LPC systems of children.