Radiation biology. Radioecology

Long-term exposure to ionizing radiation at low doses is one of the risk factors for astronauts’ health, at the same time, hematopoietic disorders caused by damage to bone marrow (BM) cells are the most common result of irradiation. The aim of this work was to evaluate the effects of chronic exposure to ionizing radiation on hematopoietic stem and progenitor cells (HSPCs) and BM stromal progenitor cells. In radiation exposure modeling, rats were exposed to 10-fold external fractionated gamma-irradiation at a total dose of 500 cGy for 33 days. The control group of animals was kept in standard vivarium conditions. The cellular composition and functional characteristics of rat femoral BM-derived cells were examined. A decrease in BM cellularity and changes in the expression of surface markers were observed after irradiation, which may indicate a disruption in the hematopoietic and non-hemopoietic cells communication. Stromal progenitor cells after irradiation were characterized by higher levels of induced and spontaneous adipogenic differentiation and reduced proliferative potential. The number of different hematopoietic colonies, except CFU-GM and the total number of colonies were decreased in the experimental group. After irradiation the culture of BM-derived cells was characterized by a higher production of cytokines, which inhibit HSPC proliferation (IL-18, IFNγ) and activate their differentiation (IL-6). There was also an increase in the expression of pro-resorptive genes and cytokines (Sost) along with a decrease in the expression of genes involved in osteogenesis. Thus, it was demonstrated that chronic fractionated irradiation in the low dose range causes negative changes in the stromal and hematopoietic BM compartment, which may lead to impaired hematopoiesis.

The aim of the work is an experimental study of the radioprotective effect of shortened recombinant flagellin under conditions of total body irradiation of mice by survival rates and the effect on hemo- and immunopoiesis. A new recombinant shortened derivative of Salmonella enterica – dFliC protein obtained by structure-oriented reengineering of a previously developed molecule was used. The radioprotective effect of dFliC was studied in the mouse model of hematopoietic acute radiation syndrome. The 30-day survival of irradiated mice was analyzed using the Kaplan-Meier method. The effect of dFliC protein on the number of splenic colony-forming units (CFU-s) and myelokaryocytes in the bone marrow, peripheral blood parameters, and the cytokine profile in the blood serum of mice was assessed. Statistica 8.0 software was used for statistical processing of the results. A purification test record for the recombinant flagellin dFliC was developed, and protein samples with a purity of 92.79% according to HPLC were obtained. Administration of dFliC at a dose of 1 mg/kg 30 min prior to 7.8 Gy X-rays increased 30-day survival of mice by 38% (p < 0.05 compared to the vehicle control). On day 9 after X-ray irradiation at a dose of 7 Gy, the number of colonies increased 2.8 times in dFliC-treated mice (p < 0.05), the viability of hematopoietic progenitor cells increased and the severity of thrombocytopenia decreased. An increase in the production of cytokines involved in hematopoiesis, IL-3. GM-CSF and IL-12p40, has been recorded. The level of proinflammatory cytokines IL-1β and IL-33 was maintained at a lower level than when exposed to radiation without dFliC. Deimmunization and structural rearrangement of the flagellin molecule did not lead to a decrease in the radioprotective effect of the recombinant protein. Radioprotective efficacy of dFliC is provided by a protective effect on bone marrow hematopoietic cells and stimulation of postradiation restoration of hemo- and immunopoiesis by regulating the expression of cytokines with a wide range of biological activity.

Currently, sufficient experimental data have been obtained indicating significant violations of the functions of the central nervous system (CNS) at all levels of its organization caused by exposure to heavy ions in doses comparable to those potentially possible during a Martian mission. An extremely important and, at the same time, the least studied problem is the neurobiological effects of the combined action of ionizing radiation and non-radiative factors of spaceflight, in particular, the most important of them-microgravity. Analyzing the neurobiological effects of the interaction of simulated microgravity (ANS) and ionizing radiation, we found their complex nature: at all levels of the central nervous system organization (from molecular to integrative), both synergistic and antagonistic relationships were observed under the combined in fluence of these factors. The possibility of the antagonistic nature of the interaction of these PCF data was a very unexpected effect that requires further research. It can be concluded that the neurobiological effects of the interaction of ANS and ionizing radiation with their synchronous combined action are complex, which we called interference, by analogy with the physical phenomenon of interference, showing synergistic or antagonistic effects, or the appearance of new effects in relation to behavior, metabolism of monoamines and molecular mechanisms. It is possible that the manifestation of this kind of interaction may lead to the leveling of negative consequences from the effects of these factors.

In this study, for the first time, information was obtained on the sensitivity of animals with dysfunction of the piwi and aub genes to chronic irradiation in low doses (20 sGy) and the manifestation of a radioadaptive response in the analyzed mutants. The reaction of mutant genotypes of Drosophila melanogaster to irradiation was analyzed in terms of lifespan, fertility, and DNA damage. The experimental results showed that females with the piwi mutation exhibited an adaptive effect of chronic irradiation in low dose (20 sGy) in response to subsequent exposure in dose 60 Gy. Chronic low-dose irradiation did not affect reproductive functions and the level of DNA damage in the gonads of individuals with dysfunction of the piwi and aub genes, but led to an increase in their lifespan. Thus, a functional decrease in some genes of the Argonaute family can modify the effects of irradiation with the formation of radioresistant traits in animals.

Exposure of seeds to a dose of γ-radiation of 20 Gy and a concentration of 2 mg/ml lead significantly modifies the oxidative status of barley plants. Lead at the concentration studied is capable of suppressing the development of seedlings, but is inferior to γ-radiation in its ability to induce cytogenetic abnormalities in the root meristem. Lead toxicity affects roots much more than shoots because roots interact directly with the lead solution. Preliminary seeds γ-irradiation modifies the oxidative status of plants, which reduces the negative effect of lead on seed germination and mitotic activity of cells. The combined action of lead and ionizing radiation does not lead to increased oxidative stress and an increase in the frequency of cytogenetic abnormalities compared to their separate action.

In the present work, the sequential combined action of the pulsed magnetic field (PMF) (carrier frequency 1.8 MHz, modulated by pulses with a repetition rate of 28 kHz, magnetic field induction at the location of biological objects 75 mT per pulse with a duration of action on seeds of 60 s) and the amplitude of g-radiation at a dose of 3 g on the meristems of cells of the original onion. The systems of cells with chromosomal aberrations in the ana-telophase, types of aberrations, mechanisms of cells with micronuclei and the mitotic index were analyzed. Gamma radiation led to an increase in the frequency of cells with chromosomal aberrations by 12 times, the frequency of cells with micronuclei by 64 times. PMF led to an increase in the frequency of cells with chromosomal aberrations by 2 times, and cells with micronuclei by 3 times. The combined action of limiting factors was characterized by antagonistic interactions. Several hypotheses have been proposed to explain the effects of the combined action of IMF and gamma irradiation: IMF is guaranteed, leading to increased efficiency of DNA repair; IMF increases the level of apoptosis of lower cells and the elimination of radiation-induced aberrant cells; IMF leads to a more pronounced delay in the cell cycle and thus increases the time for repair of radiation-induced DNA damage.