Delayed effects of chronic low-dose high linear energy transfer (LET) radiation on mice in vivo.

In the present work, the delayed effects of chronic high linear energy transfer (LET) radiation in polychromatic erythrocytes (PCEs) of mice bone marrow were investigated in vivo. Irradiation of the two-month-old SHK white mongrel random-bred male mice was performed in the radiation field behind the concrete shield of the accelerator of 70 GeV protons to accumulate doses of 0.005-0.16 Gy. The dependence of the biological response on dose, adaptive response (AR) and genomic instability (GI) in F(1) and F(2) generations from males irradiated with doses of 0.005 and 0.16 Gy and from males exposed to combined action of immunomodulator-bendazol hydrochloride (BH) and of 0.16 Gy irradiation, were examined using the micronucleus formation test. The data demonstrated that irradiation of mice with these doses lead to an increase in the level of cytogenetic damage and induces no AR. With analysis of the bone marrow radiosensitivity to 1.5 Gy of X rays and the capacity to AR it was found that the chronic high-LET irradiation of parents induced the GI at least two generations. The combined exposure to BH and the dose of 0.16 Gy induces no AR in F(0) generation but induces AR in F(1) and F(2) offspring.

101 Hz frequency-modulated infrared light induces cytogenetic adaptive response in mouse bone marrow in vivo.

The micronucleus test was used tu study the possibility of inducing cross-adaptive response in mouse bone marrow cells in vivo with an 850 nm infrared light modulated by a 101 Hz frequency, emitted by a light therapy device "Kurator". We demonstrated that this exposure led to a substantial reduction of cytogenetic cell damage produced by further exposure of animals to X-radiation in the dose of 1.5 Gy, i.e. it induced an adaptive response which did not differ by the magnitude and time course from the adaptive response to radiation.

[Study of the genetic instability in generations of mice irradiated of a low-dose rate of high-LET radiation].

In present work, we investigated the genetic instability in mice of F1, of F2 and of F3 generations born from males irradiated by a low-dose rate of high-LET radiation that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights in vivo in polychromatic erythrocytes of bone marrow using the micronucleus test. Two-month-old males of SHK white mongrel mice were used. Irradiation was performed for 24 h a day in the radiation field behind the concrete shield of the U-70 accelerator of 70 GeV protons (Serpukhov) to accumulate doses of 11.5, of 21.5 and of 31.5 cGy (1 cGy/day). The experiments demonstrated that in mice of F1 generation born from males irradiated with doses of 11.5, 21.5 and of 31.5 cGy, an increase in sensitivity to additional irradiation with a dose of 1.5 Gy of gamma-radiation and the absence of adaptive response compared with the descendants of unirradiated males occur. In contrast to F1 generation genetic instability in mice of the F2 and F3 generations was revealed only by the absence of adaptive response. These data indicate a genetic instability in F1, F2 and F3 generations born from irradiated males.

[Peculiar effects of low doses of high let radiation on mice].

Experiments with exposure of mice to low doses of chronic high-LET radiation were carried out in the radiation field behind the concrete wall of the Serpukhov accelerators of protons with the energy of 70 GeV. The goal was to study dose dependence, radiation adaptive response (AR), and genetic instability. Mice (SHK strain) were irradiated continuously 15, 24 and 31 days which corresponded to the doses of 11.5, 21.5 and 31.5 Gy. Cytogenetic damages were determined using the micronuclear test in marrow polychromatophil erythrocytes. It was shown that all the experimental doses aggravated the cytogenetic damage; however, no AR induction in marrow cells was observed. Males of the F1 generation born from the males irradiated at 11.5 Gy had same level of spontaneous cytogenetic damage as males born from non-irradiated parents. Yet, they displayed an exaggerated sensitivity to additional exposure to 1.5 Gy and no AR induction by the standard gamma-protocol which is indicative of genetic instability.

[The effect of low-dose rate radiation simulating the high-altitude flight conditions on mice in vivo].

In present work, we investigated the peculiarities of the effect of a low-dose rate high-LET radiation that simulates the spectral and component composition of the radiation field formed in the atmosphere at a height of 10 km on mice in vivo. The dose dependence and adaptive response were examined. Irradiation of mice was performed for 24 h a day in the radiation field behind the concrete shield of the Serpukhov accelerator of 70 GeV protons for the time (15-31 days) necessary to accumulate the required doses. The experiments demonstrated that irradiation of mice in vivo in the dose range of 11.5-31.5 cGy leads to an increase in cytogenetic damage to bone marrow cells and induces no adaptive response in bone marrow cells.

Peculiarities of the effect of low-dose-rate radiation simulating high-altitude flight conditions on mice in vivo.

In the present work, the effect of a low-dose rate of high-LET radiation in polychromatic erythrocytes of mice bone marrow was investigated in vivo. The spectral and component composition of the radiation field used was similar to that present in the atmosphere at an altitude of about 10 km. The dose dependence, adaptive response, and genetic instability in the F1 generation born from males irradiated under these conditions were examined using the micronucleus test. Irradiation of the mice was performed for 24 h per day in the radiation field behind the concrete shield of the Serpukhov accelerator. Protons of 70 GeV were used over a period of 15-31 days, to accumulate doses of 11.5-31.5 cGy. The experiment demonstrated that irradiation of mice in vivo in this dose range leads to an increase in cytogenetic damage to bone marrow cells, but does not induce any adaptive response. In mice pre-irradiated with a dose of 11.5 cGy, an increase in sensitivity was observed after an additional irradiation with a dose of 1.5 Gy. The absence of an adaptive response suggests existence of genetic instability.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate gamma-Irradiation.

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to gamma-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20-61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level gamma-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation.

[Low doses of radiation decrease the level of spontaneous and gamma-induced chromosomal mutagenesis in bone marrow cells of mice in vivo]. / Malye dozy radiatsii snizhaiut uroven' spontannogo i gamma-indutsirovannogo khromosomnogo mutageneza v kletkakh kostnogo mozga myshei in vivo.

Low doses of ionizing radiation are known to induce adaptive response (AR), which is characterized in most cases by temporary nature, though the possibility of long-term persistence of AR is not ruled out. In this investigation we studied the effect of low doses of gamma-radiation on both high-dose radiation-induced and spontaneous level of cytogenetic damage throughout the life of mice. SHK male mice 2 months old were used. Priming doses of 0.1 and 0.2 Gy (0.125 Gy/min, gamma-radiation from 60Co) were used. A challenging dose of 1.5 Gy (1 Gy/min) was used in the experiments using a routine AR experimental design. The frequency of micronucleated polychromatic erythrocytes in bone marrow cells of primed, primed and challenged, and control groups was assessed at various times of animal life span. It was shown that: a) single low-dose gamma-irradiation induces a cytogenetic AR which can be revealed at 1, 3, 6, 9, 12 months after priming; b) single low-dose gamma-irradiation decreases the cytogenetic damage to a level below the spontaneous rate at the end of lifetime (20 months) of animals; c) ability to induce adaptive response does not depend on the age of animals at the moment of priming irradiation. In conclusion, the mechanisms underlying AR not only protect from chromosome damage induced by high-dose irradiation but also may play a role in spontaneous mutagenesis during aging of animals.

[Estimation of genetic effects of chronic exposure to low-dose rate gamma-radiation by cytogenetic methods and DNA-comet assay]. / Otsenka geneticheskikh éffektov khronicheskogo vozdeistviia nizkointensivnogo gamma-izlucheniia tsitogeneticheskimi metodami i metodom DNK-komet.

The study of genetic effects in CBA/lac mice exposed for 1 year to constant low dose-rate gamma-radiation at a dose-rate 63 cGy/year has been carried out. We have shown the significant increase in the DNA breaks' level in spleen lymphocytes by comet-assay beginning from the total absorbed dose of 20 cGy. It is possible that the DNA breaks' level increase resulted from the structural rearrangement of chromatin or induction of lymphocyte proliferation. The results obtained by micronucleus test have proved that the mutagenic effect of chronic low dose-rate gamma-radiation depends on cell type and respectively on cell proliferation rate, cell differentiation, etc. So, by the end of experiment the significant increase in the frequency of PCE with micronuclei (MN) was observed. However, in contrast, the frequency of NCE with MN was not increased. No significant increase in the percent of lung cells with MN was registered.

[Detection of genomic instability in offspring of male mice chronically exposed to gamma-radiation by the "adaptive response" test]. / Vyiavlenie s pomoshch'iu testa "adaptivnyi otvet" nestabil'nosti genoma u potomstva samtsov myshei, podvergnutykh khronicheskomu vozdeistviiu gamma-izlucheniia.

The genomic instability (GI) in somatic cells of the progeny (F1 generation) of male mice chronically exposed to low-dose gamma-radiation was studied by comparative analysis of chromosome damage. BALB/C male mice exposed to 0.1 Gy (0.01 Gy/day) and 0.5 Gy (0.01 and 0.05 Gy/day) were mated with unirradiated females 15 days after irradiation. For comparison of radiosensitivity, two-month-old males, the descendants of irradiated and unirradiated animals, were subjected to irradiation with a dose of 1.5 Gy (0.47 Gy/min) from a 60Co source. GI was revealed by the standard scheme of adaptive response. The experiments indicated that, by using the test "adaptive response", it is possible to detect the transition of gamma-radiation-induced genomic instability in sex cells of male parent into somatic cells of mice (F1 generation) either from changes in radiosensitivity or by the absence of the adaptive response induced by a standard scheme.

[Induction of cytogenetic damages by combined action of heavy metal salts, chronic and acute gamma irradiation in bone marrow cells of mice and rats]. / Kombinirovannoe deistvie solei tiazhelykh metallov, khronicheskogo i ostrogo gamma-oblucheniia na velichinu tsitogeneticheskogo povrezhdeniia v kletkakh kostnogo mozga myshei i krys.

The aim of the present work was to study the combined action of salts of heavy metals (lead and cadmium), and acute and chronic gamma-irradiation on the cytogenetic damage to bone marrow cells of rats and mice. It was shown that the chronic exposure of rats and mice in vivo to gamma-irradiation induced the adaptive response. The salts of heavy metals supplemented to the diet of rats enhanced the cytogenetic damage to the non-irradiated animals, slightly enhanced the effect of chronic and acute gamma-irradiation, decreased the cytogenetic adaptive response induced by chronic gamma-irradiation.

[Correlation between the duration of radiation adaptive response in bone marrow cells of mice and the dose of gamma-irradiation in vivo]. / Zavisimost' dlitel'nogo sokhraneniia radiatsionnogo adaptivnogo otveta v kletkakh kostnogo mozga myshei ot dozy gamma-oblucheniia in vivo.

The dependence between the adaptive response and adaptive dose was studied on the basis of cytogenetic damage in polychromatic erythrocytes of bone marrow cells in mice after a low dose gamma-irradiation in vivo. The adaptive response to doses of 0.1 and 0.2 Gy was found to be retained for at least two months after irradiation. However, the adaptive dose of 0.4 Gy did not induce prolonged adaptive response.

[Dependence of the cytogenetic adaptive response in the rat bone marrow cells on the dose of chronic gamma irradiation in vivo]. / Zavisimost' velichiny tsitogeneticheskogo adaptivnogo otveta v kletkakh kostnogo mozga krys ot dozy khronicheskogo gamma-oblucheniia in vivo.

The induction of chromosome aberrations in bone marrow cells of rats exposed to chronic gamma-irradiation and subsequently to acute gamma-irradiation was studied. Adult male rats were exposed ot 3-40 cGy (2.9 cGy/day) of chronic gamma-irradiation (adaptive dose) and subsequently to 4 or 6 Gy of gamma-rays (47 cGy/min, challenge dose). The yield of chromosome aberrations in marrow cells induced by adaptive and challenge dose was lower than the sum of the yields separately induced by chronic and acute gamma-irradiation. The most effective dose for induction of the adaptive response was 0.4 Gy.

[Action of low doses of gamma-radiation on cytogenetic damage in polychromatophilic erythrocytes of bone marrow in mice in vivo]. / Deistvie malykh doz gamma-radiatsii na tsitogeneticheskoe povrezhdenie v polikhromatofil'nykh éritrotsitakh kostnogo mozga myshei in vivo.

The frequency of micronuclei was estimated in bone marrow polychromatic erythrocytes (PCEs) of mice gamma-irradiated in vivo at doses of 5-50 cGy. The dose-effect curve was found to have a complex stepwise pattern with three consequent segments: (1) high radiosensitivity, (2) a significant decrease in radiosensitivity, and (3) an increase in radiosensitivity.

[Induction of cytogenetic damage to rat bone marrow cells by combined exposure to chronic and acute gamma radiation]. / Induktsiia tsitogeneticheskogo povrezhdenniia v kletkakh kostnogo mozga krys pri kombinirovannom vozdeistvii khronicheskogo i ostrogo gamma-oblucheniia.

The combined influence of various doses of chronic irradiation (0.029 Gy/day) followed by acute irradiation at doses of 4 and 6 Gy (0.47 Gy/min) on the frequency of chromosomal aberrations in rat bone-marrow cells was studied. A pronounced adaptive response was observed at all doses of chronic irradiation followed by acute irradiation.