Volume 64, Nº 2 (2024)

There are different approaches to assessing the human individual radiosensitivity. In this study, individual radiosensitivity was assessed in terms of survival and recovery of human hematopoietic stem cells (HSC) after acute gamma irradiation of humanized mice. Immunodeficient NOD SCID mice were transplanted with cord blood HSC intravenously, peripheral or umbilical cord blood HSC intraosseously. The estimated D₀ value for human HSCs was 1.19 Gy (95٪ CI 0.90 to 1.74), 0.99 Gy (95٪ CI 0.87 to 1.15), and 0.93 Gy (95٪ CI 0.61 to 1.91) for the three methods of obtaining humanized mice, respectively. For all three methods of mouse humanization, statistically similar models that describe the dependence of HSC survival on the acute gamma irradiation dose in the range of 0.5—1.5 Gy were obtained. Thus, intraosseous administration of peripheral blood HSCs to immunodeficient mice can be effectively used to assess the response of human HSCs to radiation exposure. Comparison of the HSC number (CD34⁺ cells) and their descendants (CD45⁺ cells) in non-irradiated and irradiated mice humanized with cells from the same donor on days 3 and 14 after irradiation makes it possible to evaluate the processes of radiation-induced death and recovery of HSCs. A coefficient calculated as the ratio of the proportion of HSCs among all human cells in the bone marrow of humanized mice on the 14th day to the proportion of HSCs on the 3rd day after irradiation was proposed to assess the response to radiation exposure. This coefficient had an inverse linear dependence on the radiation dose, differed in mice with increased and normal radiosensitivity, and increased with the use of the radioprotector cysteamine in humanized mice. We propose to use this coefficient for a comparative assessment of human radiosensitivity.

The paper presents the results of a study of the association of single nucleotide polymorphisms of the WNT genes with an increased frequency of cytogenetic disorders in the blood lymphocytes of workers at an ionizing radiation facility exposed to long-term radiation exposure at doses of 100–500 mGy.The object of the study was the blood of 95 apparently healthy workers who were subjected to long-term technogenic external exposure to γ-radiation in doses from 100 to 500 mGy in the course of their professional activities. For all examined individuals, a standard cytogenetic analysis of blood lymphocytes was performed. Genomic DNA was isolated from workers’ blood lymphocytes using a “QIAamp DNA Blood mini Kit” (Qiagen, Germany). DNA was genotyped for 116 single nucleotide polymorphisms of the WNT genes using high-density “CytoScan™ HD Array” (Affymetrix, USA) chips (DNA chips). Taking into account the Bonferroni correction, an association of single nucleotide polymorphisms of the WNT genes with a high frequency of circular chromosomes in blood lymphocytes was established, all other types of cytogenetic disorders did not show statistical significance. As a result of the study, a single nucleotide polymorphism of the WNT9B gene rs1530364 was identified, which can be considered as a potential marker of individual radiosensitivity.

The paper presents the development, assessment of the safety and antiradiation activity of a therapeutic agent based on the culture of Escherichia coli strains “PL-6” and “KV-1”. To obtain the antiradiation agent, the causative agent of colibacillosis was grown in meat-peptone broth in a thermostat at a temperature of 37°C for 3 days. The grown suspension was centrifuged at 3000 rpm for 50 min, the supernatant was decanted. The sediment was brought to 1 billion cm³ with distilled water. Smears were prepared from the grown cultures and stained according to Gram to determine the purity and species of the grown culture. The prepared suspension was poured into sterile vials of 10, 50 or 100 cm³, sealed with rubber stoppers and rolled with aluminum caps, labeling with an indication of the strain, radiation dose and date. Irradiation of the microbial material was carried out on the γ-installation “Issledovatel”, source ⁶⁰Co, absorbed dose rate of 1.028 Gy/sec, in the ranges of absorbed doses from 7.5 to 30.0 kGy with interdose intervals of 2.5 and 5.0 kGy. The degree of inactivation of γ-irradiated E. coli cultures was determined by seeding them on meat-peptone agar and thermostatting for 168 hours, recording the presence or absence of microorganism growth. The studies have established that the timing and degree of growth of irradiated E. coli cultures of the “PL-6” and “KV-1” strains are directly dependent on the radiation dose, their complete inactivation occurs with irradiation at a dose of 25.0 kGy. Further studies have shown that the developed biopreparation obtained on the basis of E. coli is sterile, areactogenic, non-toxic and harmless. The mechanism of formation of radioresistance of the organism against the background of application of antiradiation agents based on E. coli strains “PL-6” and “KV-1” consisted in restoration of hematological, biochemical and immune parameters, which contributed to preservation of 66.7 to 83.3٪ of lethally irradiated animals.

The aim of this study was to search for the specific morphological features of radiation-induced lung fibrosis compared to pulmonary fibrosis of another origin, using biological specimens of lung tissue collected from workers internally exposed to alpha radiation. The morphological features of lung fibrosis were defined using biological specimens of lung tissue that had been collected during autopsy examinations from 56 workers diagnosed with plutonium-induced lung fibrosis during life, from 34 workers with lung fibrosis of another origin (due to chronic inflammatory lung diseases) and from 35 workers without clinical pulmonary pathology (controls). The total lung-absorbed dose of gamma radiation from external exposure did not significantly differ among the studied groups, and the total lung-absorbed dose of alpha radiation from internal exposure was significantly higher in workers with plutonium-induced lung fibrosis. To investigate the extracellular matrix components, mono- and polyclonal labeled antibodies against type I, IV, and V collagens were used. In addition, to evaluate the system of extracellular matrix metabolism regulation, the antibodies against matrix metalloproteinases MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 were used. The study revealed qualitative and quantitative morphological peculiarities of plutonium-induced lung fibrosis compared to lung fibrosis of another origin. This allows us to conclude that plutonium-induced lung fibrosis is a specific type of lung fibrosis, which is characterized with specific location and architectonics of fibrosis foci within the lung, and with changes in levels of collagen, elastic and reticular fibers in the pulmonary stroma. The analysis demonstrated that hyperproduction of type V collagen plays a key role in the development of plutonium-induced lung fibrosis. In addition, the imbalance between the expression of MMPs and their inhibitors plays an important role in the development of lung fibrosis.

Assessing the role of social factors in the formation of radioresistance in chronic exposure and finding ways to increase it are important for understanding the mechanisms of the damaging effects of radiation and developing practical methods for reducing radiation risk in professionals exposed to ionizing radiation and patients undergoing radiation therapy. In this work, we investigated the ability to influence the lifespan of animals exposed to γ-radiation fractionally for a long time by replacing drinking water from tap water to distilled water. Female ICR mice (CD-1) were exposed to total ⁶⁰Co γ radiation weekly in fractions for 33 weeks starting at 9 weeks of age. The dose of a single irradiation was 50 mGy, the average dose rate was 2 mGy/sec. The total radiation dose was 1.65 Gy. Control non-irradiated mice and irradiated animals were divided into 2 groups. The first received tap water, and the second received distilled water throughout the experiment. Non-irradiated animals kept on tap water showed a statistically insignificant (log-rank test, p = 0.483) reduction in average life expectancy compared to mice kept on distilled water. In animals after exposure to ⁶⁰Co γ-radiation, a statistically significant (p = 0.0013) decrease in life expectancy was noted when kept on tap water and statistically insignificant (p = 0.1511) when kept on distilled water. Tap water and irradiation showed a clear synergy with a combined effect on the body of mice, expressed in a more than threefold decrease in the period of post-radiation shortening of life expectancy. Distilled water reduced the rate of death of irradiated animals and modified the rate of death of non-irradiated animals. Our data demonstrate that the reduction in life expectancy of mice kept on tap water caused by long-term fractionated irradiation can be reduced when animals are kept on distilled water.

In the vegetation experiment, the plutonium, micro- and macroelements migration in the “soil–agricultural plant” system depending on soil moisture in the range from 15 to 40٪ of absolute soil moisture were studied. The content of ²³⁹Pu was analyzed by α-spectrometry with preliminary radiochemical isolation. The elemental composition was analyzed by the ICP-MS and ICP-AES methods. Beans (Fabaceae) variety “Amber” were used as a test culture. The plutonium transfer factor obtained in the vegetation experiments are in the range of of 5.3×10^–4–1.5×10^–2, with an average value of 5.4×10^–3 for the aboveground part of bean and range of 4.5×10^–2–2.7×10^–1, with an average of 1.6×10^–1 for bean roots. It was determined that the distribution of plutonium, micro and macro elements in the vegetative organs of plants is not equally, the transfer factor of plutonium for the aboveground part of plants is lower than for the root part. It has been established that the accumulation of plutonium, micro- and macroelements, depending on soil moisture, is different for the organs of beans. The dependence of plutonium accumulation by plants on soil moisture is significantly higher than for other considered elements. A decrease in the coefficient of accumulation of plutonium in the aerial part of the beans is recorded with an increase in soil moisture up to two orders of magnitude. There is a trend towards a slight decrease in the accumulation coefficients of Fe, Mg, Mn, Cr, Mo, Ni, Co, Cu. For the root system of beans, a clear dependence of the accumulation of the considered elements on soil moisture is not observed.