Radiation biology. Radioecology

The effect of ionizing radiation on the body in the form of structural lesions at the cellular level, primarily DNA (chromosomal aberrations), cell membranes, mitochondria and other substructures causes release of many high-molecular compounds of various nature with antigenic properties from the cell into the blood and lymph flow. They can be a highly mobile group of proteins, damaged nuclear and mitochondrial DNA, extracellular ATP, oxidized low-density lipoproteins and other products that contribute to the development of primary radiation stress with the activation of free radical peroxide processes and subsequent inflammatory reaction. With a certain high radiation load (from 20 to 50 Gy), primary radiation toxemia determines the thanatogenesis of acute radiation disease, which is clinically presented as a toxemic form. Since the early works, there has been a search for substances (radiotoxins) that cause mainly a picture of radiation toxemia. These included compounds of a quinoid nature, lipid peroxide products (works of the 60–70 years of the last century by A.M. Kuzin and Yu.B. Kudryashov). Over the past decades, V.M. Maliev’s fundamental research on large animals has identified a group of high-molecular compounds from a number of glycoproteins in the form of radiotoxins that experimentally reproduce all types and forms of acute radiation disease, including toxemic form and cerebral syndrome in the absence of radiation exposure, and for each form of radiation damage they are organ-specific. Attention is drawn to the high anti-radiation efficiency of screening the abdominal area, where the contribution of hematopoietic tissue protection is very limited which allows us to conclude about the high adverse contribution of “intestinal toxemia” to the development of a typical form of acute radiation disease. The significance of this factor in the thanatogenesis of acute radiation disease is especially pronounced when the anti-radiation effect of radioprotectors is potentiated by screening the abdomen. According to the results of studying the anti-radiation features of the emergency radioprotector indralin in experiments on dogs, DRF of the drug at a dose of 10 mg/kg increased from 2 to 5, i.e. 2.5 times.

Cytokines are proteins produced by various cells of the body and are intercellular messengers. They perform many functions that are very important for understanding the pathogenesis of early and late effects of exposure, their prevention and treatment. The purpose of this work was to study the cytokine profile in individuals exposed to chronic occupational exposure. The main group consisted of employees of the Mayak nuclear industry enterprise who were exposed to chronic exposure as a result of their professional activities. The control group consisted of residents of the city of Ozyersk, Chelyabinsk region, who were not exposed to chronic exposure as a result of their professional activities. The study used enzyme immunoassay, which was carried out in accordance with the instructions of the manufacturers of the test systems. Statistical analysis of the obtained data was carried out using the Mann–Whitney method. Serum levels of IFNγ and TNFα were increased in the occupationally exposed group. In addition, it was found that the content of IL-18 и IL-35 in blood serum increased with an increase in the dose of internal α-irradiation to the red bone marrow (RBM), and the concentration of IL-17А, IL-35 и TNFα – with an increase in the dose of external irradiation on the RBM. External γ-irradiation suppressed the expression of IL-27 in the blood serum of workers. The content of anti-inflammatory cytokines in the blood serum of exposed individuals was not changed. The results obtained allow us to conclude that the expression profile of the studied cytokines was shifted to the inflammatory side in the long-term period after the end of occupational exposure.

This paper presents the results of using three-color FISH-staining of chromosomes (DNA probes for chromosome pairs 1, 4, and 12) to study the control level of translocations in peripheral blood lymphocyte cultures of 35 relatively healthy volunteer donors aged from 21 to 72 years. Such information is necessary for the retrospective establishment of both the fact of overexposure itself and for an adequate assessment of the dose received. Translocations made up the bulk of the recorded colored rearrangements. Their frequency was significantly 3.3 times higher than the level of unstable aberrations (dicentrics and acentrics). At the same time, a moderate correlation was observed between the level of FISH translocations and the age of the donors, and gender did not affect this indicator in any way. Also, no significant effect of various types of medical diagnostic radiation, smoking and the disease of the new coronavirus infection COVID-19 on the studied index of chromosome damage was found. In general, the detected frequencies of translocations in genome-equivalent cells in their relationship with age were in fairly good agreement with the results of international studies.

Hyperthermia is used in combination with radiation therapy to enhance the radiation response of the target tumor. However, heating of cancer cells activates the HSF1 transcription factor in them and stimulates the HSF1-dependent induction of heat shock proteins (HSPs), which can significantly impair the antitumor effects of hyperthermia and radiation exposure. The aim of this study was to examine the possibility of enhancing the radiosensitizing effect of hyperthermia on cancer cells by suppressing the HSF1-mediated HSP induction in them. The object of the study were HeLa cells derived from a malignant tumor of the human cervix. Before irradiation (2–7 Gy), cells were subjected to heat stress (42°–44°C for 20–60 min) without or in the presence of HSF1 transcriptional activity inhibitors (quercetin, triptolide, KRIBB11). In certain cell samples, HSF1 expression was preliminarily knocked down using small interfering RNAs. Cell death and survival was assessed by the levels of apoptosis/necrosis and clonogenic ability. Expression of HSF1 and HSP was analyzed by immunoblotting. It was found that, compared with the radiosensitizing effects of hyperthermia alone, the combined treatment (HSF1 activity inhibition or HSF1 knockdown + heating) significantly increased the thermo-radiosensitization of cancer cells; this was manifested in the intensification of their post-radiation death (apoptosis + necrosis), as well as in a decrease in clonogenicity. This enhancement of thermo-radiosensitization was observed under the HSP induction blockade. Thus, the combination of hyperthermia with inhibitors of HSF1 activity or expression can effectively sensitize thermoresistant and radioresistant tumors to radiation therapy.

In this work, it is shown that irradiated polychromatophilic and normal chromatophilic peripheral blood erythrocytes of mice are able to transmit extracellular signals to non-irradiated “bystander” cells when animals are kept together. A decrease in radiation-induced changes in irradiated cells upon contact with unirradiated “ bystander “ cells is defined as a “rescue effect”. The experiment used jointly kept non-irradiated and irradiated mice that were exposed at a dose of 3 Gy on a research radiobiological gamma facility with 4 sources of ¹³⁷Cs. The frequency of polychromatophilic erythrocytes with micronucleus, normal chromatophilic erythrocytes with micronucleus, the total number of erythrocytes with these genome damages in peripheral blood on the 3rd, 7th, 14th, 30th, 60th and 90th days after irradiation was assessed using the micronucleus test. Statistical analysis was carried out using the Student’s t-test. A statistically significant decrease in the frequency of erythrocytes with micronucleus was found in irradiated animals compared to t₂ (gamma control): on the 3rd day after the start of the experiment when kept in one cage without a septum (t₂ = 2.35; p = 0.03); on the 14th day as in the group where the animals were kept without a septum (t₂ = 6.03; p = 0.000011), and in a group with a partition (t₂ = 3.29; p = 0.004); on the 60-th day in the group of animals kept without a septum (t₂ = 2.8; p = 0.01). The result may indicate that contact between irradiated and non-irradiated mice leads to a decrease in the number of damaged cells in the irradiated animal, which can be referred to as the “rescue effect”. On day 14, non-irradiated “bystander” mice kept with irradiated mice in a septal cage showed a tendency to exceed the frequency of micronucleated erythrocyte indicators in biocontrol (t₁ = 1.79; p = 0.9); on the 60th day, in non-irradiated “bystander” mice kept with irradiated mice in a cell without a septum, there was also a tendency to exceed the frequency of micronucleated erythrocyte indicators in biocontrol (t₁ = 1.39; p = 0.18). Based on the data obtained in this work, it is assumed that the discovered “rescue effect” can be used as a test for reducing the level of the damaging effect of radiation and post-radiation cell recovery.

Evaluation of ionizing radiation impact on life expectancy rates in humans is one of the topical problems of the radiation medicine. The present study aimed to analyze survival rates and the life potential loss in workers of the Mayak PA after the acute radiation sickness due to radiation accidents and in radiation accident participants who had not suffered from the acute radiation sickness. The analysis considered 64 workers of the Mayak PA (54 males and 10 females), and it was performed using the STATISTICA 10 software. We evaluated survival rates prior to and after the main disease that had caused death, percentages of individuals who had not survived to 40, 60, 80 and 80+ years, and total, partial and single (weighted means) life potential loss and the index of the life potential loss. The analysis revealed that workers with severe and extremely severe acute radiation sickness demonstrated deteriorated survival rates and the increased life potential loss compared either to workers with moderate and modest acute radiation sickness or to radiation accident participants. The cause for such estimates in workers with severe and extreme severe sickness was the extreme course of the sickness. In cases of the severe sickness, the shortening of life duration was caused mainly by the preliminary death from malignant neoplasms and the acute radiation sickness. We observed the linear regression association of survival rates and life potential loss with 1 Ln of radiation dose. The relative risk of deterioration of the survival rate and the increase of the life potential loss was considerably higher (3.64-52.0 times, p < 0.05–0.001) in workers with the severe and extreme severe acute radiation sickness acutely exposed at higher doses (above 5 or 120 Gy) compared to other workers.

In two vegetation experiments on barley plants, the effect of separate and combined UV-B, UV-A and γ-irradiation in different doses was studied for the varieties “Zazersky 85” and “Vladimir. The plants were assessed for flavonoid content, photosynthetic pigments, morphology parameters and yield. The daily dose of chronic UV-B-irradiation was 9 kJ/m², chronic UV-A – from 7.2 to 72 kJ/m², single γ-irradiation 2 and 4 Gy. It has been shown that spring barley varieties “Zazersky 85” and “Vladimir” differ in their sensitivity to chronic UV-B irradiation. When predicting the negative impact of UV-B radiation on plants, it is necessary to take into account the existing level of UVA radiation, since their effect is not additive. Stimulation of biomass growth under chronic UV irradiation may be accompanied by suppression of plant productivity. The response of barley plants to γ-irradiation can be significantly dependent on the level of UV-(A+B) radiation. In general, the dose-dependent effect of chronic UV and γ-irradiation can be considered as a transition from austress to distress and its irreversible disruption. The data from this study may be relevant for programs to develop new varieties of spring barley that are resistant to elevated levels of solar UV radiation.

A mathematical model of radionuclide migration in freshwater bodies and dosimetric models for estimating exposure of the aquatic organisms (phytoplankton, zooplankton, zoobenthos and fish) are presented. The results of reconstruction of radiation doses to aquatic organisms living in non-current Uruskul Lake, located in the near zone of the Kyshtym accident are presented. The contributions of various radionuclides, as well as internal and external exposure to the formation of doses to aquatic organisms during 50 years after radionuclides entering the body of water are estimated.