[Cytological and cytogenetic studies of cells of Mongolian gerbils' retinal epithelium and marrow following 12-day space flight].

The paper report the results of studying mitotic activity and cytogenetic disorders in marrow and retinal epithelium cells of Mongolian gerbils in 21 - 23 hrs. of landing space apparatus Foton-M3, and the animals of synchronous and vivarium controls. Cells of the space flown gerbils displayed a statistically significant (p < 0.05) gain in the ratio of mitosis prophases and metaphases to the sum of ana- and telophases (1.7 +/- 0.3 and 2 +/- 0.1, respectively) as compared to these parameters in the synchronous and vivarium controls, where the ratio made up 0.6 +/- 0.1 and 0.7 +/- 0.1, respectively. Frequency of aberrant mytoses in the form of bridges was increased equally in both types of cells. Patterns of chromosome damages occurred in flight infer that the major portion of changes was not due to chromosome breakage but adhesion and ensuing wrong disjunction. These results seem to have been caused by acute g-stress to organism during re-entry and return from micro-g to the normal gravity.

[Cytogenetic analysis of cosmonaut's blood lymphocytes exposed to low space radiation doses and its place in clinical-physiological health monitoring].

The article discusses the informative significance and pertinence of cytogenetic analysis of peripheral blood lymphocytes to the clinical-physiological investigations of cosmonauts conducted before and after space missions (SM) of varying duration. The authors point out high sensitivity of the technique, relative simplicity and affordability of the analysis of instable chromosomal aberrations including such radiation effect markers as dicentrics and centric rings. Cytogenetic investigation of cosmonauts could be used to estimate ionizing radiation dose, and to predict delayed effects.

[Cytological and cytogenetic damages of spermatogonial cells in mice in the acute and late periods after irradiation by protons, helium ions, and gamma-rays].

Experiments with small test animals have been carried out to study the survival rate of spermatogenic cells in the acute period after exposure to protons with the energy 9 GeV, helium ions with the energy 4 GeV/nucleon, and 60Co gamma radiation in doses of 0.5-7.5 Gy and the reciprocal translocation frequency in spermatocytes under meiosis at the diakinesis-metaphase-1 stage six months after the exposure of the animals to protons with the energy 50 MeV and 9 GeV, helium ions with the energy 4 GeV/nucleon, and 60Co gamma-radiation in doses of 0.5-4.0 Gy. It is shown that the dependence of the effect on the dose is linear or near to linear for all kinds of radiation used. Relative biological effectiveness coefficients of the accelerated nuclei obtained by correlating equally effective doses of the standard and investigated radiations turned out to be higher in survival rate of type B spermatogonium and amounted to 2.0 and 1.3 for 9 GeV protons and helium ions respectively. At the same time, the use of the nonparametric method to determine the RBE coefficients in the course of finding out the reciprocal translocation frequency in spermatocytes points to an increase in the RBE coefficients of charged particles from 1.0 to 2.0.

[Chromosomal aberrations upon isolated and combined exposures to chemical substances and ionizing irradiation].

The partial summation of biological effects evaluated by the anaphasic chromosomal aberration test in the bone marrow karyocytes of mice was determined when the animals were concurrently exposed to chemical substances (acetone, acetaldehyde, ammonia, and ethanol) at low concentrations and gamma-irradiation in a total dose of 30 Gy. Qualitative analysis of chromosomal aberrations in the karyocytes of the bone marrow (ponses, fragments) has indicated that upon combined exposure of the animals to the chemical substances and gamma-irradiation, the chemical factor is dominant since upon combined radiochemical exposure, the number of chromosomal aberration increases mainly at the expense of fragments (91.2%), as does upon isolated exposure to chemical substances (96.4%).

[Cytogenetic effects on blood lymphocytes of cosmonauts after low doses of space radiation].

Cytogenetic changes in cultures of blood lymphocytes from 37 cosmonauts returned from space flights of varying duration were analyzed. Prolonged stay in space was shown to increase numbers of stable and unstable chromosomal aberrations. Frequency of dicentric and centric rings depends on flight duration, as well as values of accumulated dose from and dose rate of space radiation. Egress into open space leads to an additional growth in the number of chromosomal aberrations. It was found that frequency of chromosomal aberrations in blood lymphocytes remains altered even after several years of cosmonaut's return from space flight. Based on the counts of symmetric translocations obtained with the FISH-technique, mean dose from space radiation following the maiden prolonged space flight amounted to 110 mGy which is in agreement with the biodosimetric data about frequency of dicentric and centric rings (140 mGy).

[Cytogenetic and biochemical reactions of experimental animals to combined exposure to low-intensity radiation and chemical factors].

Combined exposure of mice to a mixture of chemicals in small quantities and gamma-radiation at a total dose of 30 sGy cause partial summation of biological effects assessed by cytogenetic disorders in nuclear cells of the bone marrow and changes in erythrocyte metabolism. The level of cytogenetic damages in bone marrow cells remained increased till day 14 of recovery, whereas following exposure to chemicals or radiation alone the number of chromosomal aberrations (ChA) was nearly same as in control at this point of recovery The anaphase method showed prevalence of ChA in the form of fragments over bridges in marrow karyocites. The combination of factors suppressed energy-producing processes in erythrocytes (reliable reductions in lactate dehydrogenase and lactate) and activated oxidation processes (reliable decrease in reduced glutathione). Functional shifts in erythrocyte metabolism persisted till day 30 of recovery Based on results of the investigation, functional status of organism following low-intensity exposures can be assessed, along with cytogenetic, also by indices of erythrocyte metabolism.

[Cancinogenic effects of fast helium ions with energy of 4 GeV/nucleon in rats].

The study was made of carcinogenic efficiency of 4 GeV/nucleon helium ions (LET = 0.88 keV/um) in comparison with gamma-radiation 60Co (LET = 0.23 keV/um). Adult outbred female rats underwent a single whole-body irradiation with helium ions in doses 0.25-4.0 Gy at the Synchrophasotron of the Joint Institute for Nuclear Research and with gamma-rays at "PX-gamma-30" irradiator in doses ranged from 0.5 to 4.0 Gy. The yields, histology and occurrence time of hemoblastoses and tumours in mammary glands, in endocrine glands, in soft tissues and in other organs were determined. Histological study was made using conventional methods. The irradiation of experimental animals with accelerated helium ions and standard radiation was shown to result in an increase in the yield of growths of various localizations with decreasing occurrence time and expanding histological spectrum as compared with intact rats. However, helium ions possess a higher carcinogenic efficiency. The coefficients of relative biological effectiveness of helium ions calculated by the nonparametric method appeared to increase with decreasing the radiation dose.

[Relative biological effectiveness of accelerated heavy ions and fast neutrons estimated from frequency of aberration mytoses in the retinal epithelium].

Analyzed was the literature and authors' experimental data concerning lesion and recovery of epithelium cells of mice retina immediately and long after irradiation at different sources including single and partly fractionated irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron ions, and fast neutrons of the reactor range in a large spectrum of doses and LET. Reviewed are some new techniques of determining the RBE coefficient for these types of radiation; large values of the RBE coefficients for accelerated ions and neutrons (5-10 times higher than RBE coefficients calculated for the next day following irradiation) are a result of integration into calculation of the available data about the delayed disorders in retinal epithelium cell regeneration.

[Experimental studies of the relative biological effectiveness of accelerated charged particles varying in energy].

Experimental results and literary data were analyzed for the relative biological effectiveness of heavy charged particles in a broad range of energy and LET to cells of humans and other mammals in culture, whole body of laboratory animals, microorganisms, bacteriophages, and plants. Analyzed were data obtained with the use of a diversity of tests of acute and delayed lesions induced by ionizing radiation, cancers and cataracts, specifically. Non-parametric methods are applied in parallel to the classic method of calculating the coefficients of relative biological effectiveness by correlating the equal-effective doses of the standard and a given radiation. Consideration is given to factors that may modify RBE values estimated for different types of radiation.

[Effects of low-dose accelerated charged particles of varying LET on cytogenetic changes in comeal epithelium cells in mice]. / Vliianie nizkikh doz uskorennykh zariazhennykh chastits s razlichnymi LPE na tsitogeneticheskie izmeneniia v kletkakh épiteliia rogovitsy myshei.

Effects of low-dose heavy charged particles (HCP) of varying LET on quantitative and qualitative changes in chromosomes of the comeal epithelium cells were studied in mice. Cytogenetic damages in the comeal epithelium cells were analyzed after irradiation by ions of helium and carbon with an energy of 300 MeV/nucleon (LET = 1.36 and 12.6 keV/microm), and 137Cs gamma-rays with the doses from 5 to 200 Gy. Accelerated nuclei were shown to be more effective. On the basis of aberrant mitosis rate, RBE values for helium and carbon ions in 24, 72 and 120 hrs. after irradiation were 6.0; 3.6 and 2.2 for helium ions and 7.0; 3.8 and 2.4 for carbon ions, respectively. The dose region of 20-30 Gy turned to be dose-independent. It was established that the period of chromosomal aberration sustenance in cells is also LET-dependent.

[Carcinogenic effects of single total-body irradiation with accelerated charged particles and gamma rays]. / Kantserogennye éffekty odnokratnogo obshchego oblucheniia uskorennymi zariazhennymi chastitsami i gamma-luchami.

The study deals with the frequency of tumorigenesis in the endocrine glands, skin, soft tissues and internal organs of sexually mature female rats, exposed to accelerated charged particles with low LPE, such components of cosmic radiation as 645 MeV and 9 GeV protons and 4 GeV/nuclon ions of helium. The experiment continued until the animals' natural death. We established a high frequency of endocrine and uterine tumors and a comparatively wide range of localizations in rats which had received sufficient doses of gamma radiation. There were no intestinal or renal tumors, while very few tumors of the skin and soft tissues were detected in unexposed animals.

[Comparison of risk of mammary tumors developing in rats exposed to high-energy accelerated particles and gamma-ray radiation]. / Sravnitel'nyi risk razvitiia opukholei molochnykh zhelez u krys, obluchennykh uskorennymi zariazhennymi chastitsami vysokikh énergii i gamma-luchami.

The frequency of tumorigenesis was investigated in the mammary glands of noninbred female rats and Wistar rats, after total-body exposure to a single dose of 60CO gamma radiation, 645 MeV and 9 GeV protons and 4 GeV/nuclon ions of helium. It was found that the relative biological effects of accelerated charged particles was significantly higher. This finding was obtained from calculations of the frequency of mammary tumors.

[Effect of space flight factors on health of cosmonauts in the near and late term after space flights]. / Izuchenie vliianiia faktorov kosmicheskogo poleta na zdorov'e kosmonavtov v blizhaishie i otdalennye sroki posle kosmicheskikh poletov.

Cytogenetical studies of cosmonauts' peripheral blood lymphocytes after space flights on MIR orbital station showed a statistically significant increase in the yields of radiation-induced chromosomal aberrations. However, similar studies with in vitro irradiation of biological objects with accelerated charged particles are of great importance for elucidation of the nature of cytogenetical damage induced in vivo. It is also important to investigate the structure of cosmonatus' diseases over their life, in particular, lens opacities and oncological diseases. Thus, the purpose of the investigations planned is to study cytogenetical damage in blood lymphocytes from cosmonauts after space flights on the ISS in vivo, as well as in donor blood lymphocytes after in vitro exposure to accelerated charged particles. The tasks of the project are as follows: determination of the yields and types of chromosomal aberrations in cosmonauts' blood lymphocytes before and after space flights, comparative studies of biological effects induced in vitro by different types of ionizing radiation in human blood lymphocytes in ground experiments, assessment of cytogenetical risks, analysis of the structure of cosmonatus' diseases comparing with that of whole population, study of the mortality and frequency of cataracts and oncological diseases in cosmonauts. The results to be obtained will be used for setting of health norms applied to the influence of radiations of different types, and for elaboration of measures to reduce health risks from space flight factors.

[Probability of lens opacity and mature cataracts due to irradiation at various LET values]. / Veroiatnost' razvitiia pomutneniia khrustalika i obrazovanie zrelykh katarakt pri deistvii izluchenii s razlichnymi znacheniiami LPE.

The paper reviews experimental and clinical data on the incidence of opacity of the lens and cataract development in animals and humans due to exposure to different types of radiation. Cataractogenous effectiveness of fast neutrons, accelerated ions of carbon, helium, neon and argon with the energy of 300 MeV/nucleon, and 137Cs gamma-radiation was compared. Analysis of the incidence of opacity of the lens in consequence of low doses gave high RBE estimates (from 10 to 40). The extremely high cataractogenous effectiveness of accelerated ions makes on thing that the existent space radiation limits, particularly in part of the GCR effects on the lens and permissible doses for cosmonauts, should be reconsidered towards mitigation. The authors discuss issues of threshold radiation doses that do not markedly increase incidence and rate of the lens opacity development in the post-exposure period.

[Cytogenetic studies of blood lymphocytes of cosmonauts after long-ter, space flights]. / Tsitogeneticheskie issledovaniia limfotsitov krovi kosmonavtov posle dlitel'nykh poletov.

An analysis was performed of unstable chromosomal aberrations in peripheral blood of 36 cosmonauts after long-term space missions on "Mir" orbital station. 25 cosmonauts were examined before their flights to score spontaneous yields of cytogenetical damage. In all cases the doses absorbed by crews during space flights did not exceed permissible levels of irradiation, adopted for cosmonauts. The frequencies of chromosomal-type aberrations after space missions were found to increase significantly compared to the pre-flight levels. The yields of dicentrics and centric rings on the average were as high as 0.12 +/- 0.02 and 0.47 +/- 0.06% before and after the 1st flight, 0.18 +/- 0.05 and 0.71 +/- 0.11% before and after the 2nd flight respectively. During the inter-flight periods, usually lasted 1.5-2 years, the yields of chromosome damage lowered, but did not reach their spontaneous values. After each next flight the yields of chromosome aberrations increased again. The cytogenetical damage detected in cosmonauts' peripheral blood lymphocytes after chronic action of low doses of space radiation points out a possible increase in risks of stochastic effects in distant future for crews after long-term space missions.

[Morphological changes in the central nervous system of animals depending on the dosage and time elapsed after exposure to low let radiation]. / Morfologicheskie izmeneniia v tsentral'noi nervnoi sisteme zhivotnykh v zavisimosti ot dozy i dremeni posle vozdeistvii izluchenii s razlichnymi znachemiiami LPE.

Analytical review of the morphological investigations of cerebral cortex neurons of various animals shortly after exposure to X- and gamma-radiation was made. Considered were data of qualitative and quantitative analyses of dystrophic changes in neurons of the sensorimotor cortex of the large cerebral hemispheres of rats immediately and a long period since X-irradiation. Results of the quantitative analysis of structural disorders in the central nervous system neurons suggest radiation-produced damages early after exposure of animals to relatively low doses. Higher incidence of irreversible changes in neurons of the experimental animals, as compared with intact controls, was stimulated by the doses of no more than 0.25 to 1.0 Gy. The relative number of structural disorders in neurons and percentage of irreversibly impaired cells rose proportionally to the dose growth and further delay of the time of investigation. Possible mechanisms of delayed disorders that led to a massive building-up of the number of dystrophic neurons following 3 to 4 months post irradiation of rats are discussed.

[Substantiation of radiation quality coefficient dependence on LET in application to the assessment of early radiobiological effects]. / Obosnovanie zavisimosti koéffitsientov kachestva izluchenii ot LPE primenitel'no k otsenke blizhaishikh radiobiologicheskikh éffektov.

Radiobiological studies targeted at determination of the coefficients of relative biological effectiveness (RBE) of various radiations in comparison with the standard X-ray radiation at 180-250 keV maximum were reviewed. Comparison of reactions of the body as a whole and its specific systems shortly after acute irradiation revealed the character of the relationship of RBE coefficients to LET. These data are essential for more careful estimation of radiation risk during space missions when, in parallel with chronic exposure to determinant sources, i.e. GCR and ERB, crew members may be also subjected to comparatively brief SCR attacks, particularly during solar proton events with high fluences.

Biodosimetry results from space flight Mir-18.

Astronauts are classified as radiation workers due to the presence of ionizing radiation in space. For the assessment of health risks, physical dosimetry has been indispensable. However, the change of the location of dosimeters on the crew members, the variation in dose rate with location inside the spacecraft and the unknown biological effects of microgravity can introduce significant uncertainties in estimating exposure. To circumvent such uncertainty, a study on the cytogenetic effects of space radiation in human lymphocytes was proposed and conducted for Mir-18, a 115-day mission. This study used fluorescence in situ hybridization (FISH) with whole-chromosome painting probes to score chromosomal exchanges and the Giemsa staining method to determine the frequency of dicentrics. The growth kinetics of cells and sister chromatid exchanges (SCEs) were examined to ensure that chromosomal aberrations were scored in the first mitosis and were induced primarily by space radiation. Our results showed that the frequency of chromosomal aberrations increased significantly in postflight samples compared to samples drawn prior to flight, and that the frequency of SCEs was similar for both pre- and postflight samples. Based on a dose-response curve for preflight samples exposed to gamma rays, the absorbed dose received by crew members during the mission was estimated to be about 14.75 cSv. Because the absorbed dose measured by physical dosimeters is 5.2 cGy for the entire mission, the RBE is about 2.8.

Immune organs and haemopoietic system under modelling of the mission factors.

Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model area given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated.