Influence of the chronic gamma-irradiation at the low doses during the near ontogenesis periods on the oxidative processes in rodent organs

It is shown that the effect of the low intensity gamma-irradiation at the dose of 5.5 cGy during the 4 months including the antenatal period causes the most substantial changes of the peroxide content in the liver and in brain lipids and of TBA-reactive substances amount in organs and blood plasma of tundra vole F2 which are reproduced from parents during long-term inhabiting on the Ra-contaminated area in the Komi Republic. The consequences of the chronic gamma-irradiation at the doses of 4 cGy (the dose rate is 5 mR/h) and 31 cGy (the dose rate is 40 mR/h) are studied by the morphophysiological and by biochemical parameters in organs of mice CBA (males) within 3 months after exposure. The change of the scale of the interrelation between the liver and body masses and also between the sums of the more easily to the more poorly oxidizable fractions and the phosphatidyl choline to phosphatidyl ethanolamine ratio in the liver phospholipids in groups of the irradiated mice is found as compared with that in the control group. The absence of interrelation between the lipid peroxidation process intensity and the catalase activity in the murine liver and also between the disbalance of the biochemical functions and the dose rate and/or the dose of the gamma-irradiation is revealed. The analysis of the data obtained allow to conclude that the chronic gamma-radiation under low intensity has the systemic effect on the animal organism causing of its function on the other level.     

Development of radiation injuries and recovery processes in the hematopoietic tissue of mice after repeated exposure to fast neutrons and gamma-irradiation

A study was made of the number of CFUs and karyocytes in thigh bone and the concentration of functional cells in the peripheral blood of mice subjected to fast neutron- and gamma-irradiation four times at a 60-day interval (210 cGy per fraction). The regenerating potential decreased and the half-recovery time T1/2 increased in the haemopoietic tissue as the number of fractions and total absorbed dose increased. The dependence of T1/2 on the equivalent radiation dose was as follows: T1/2 = T1/2(0)e0.0009D.     

The antiradiation properties of the ecdysteroid-containing compounds

The antiradiation properties of the ecdysteroid-containing preparations ("serpisten" and inokosterone) are studied under their application before or after the 22.6 cGy chronic low intensity gamma-irradiation of mice. It is shown that the antiradiation of these compounds depend on the dose of preparations and time of the application before or after irradiation of mice. "Serpisten" prevented the decrease of the growth of the body mass of irradiated mice. The normalization of the phospholipid composition of the mice liver and blood erythrocytes for the most investigated parameters revealed under the application of this compound at the dose of 50 mg/kg after the irradiation of animals. The capacity of "serpisten" to decompose of peroxides is shown in vitro. Inokosterone had the certain anabolic properties, caused the normalization of the total peroxidase activity of blood and intensity of the lipid peroxidation (LPO) in brain and in liver, and also the repair of the interrelation between the LPO intensity and catalase activity in the irradiated mice liver. The obtained results allow to conclude that the antiradiation properties of the ecdysteroid-containing preparations under the chronic low intensity irradiation of animals at the low dose due to their capacity to depend on the LPO regulatory system parameters.     

The role of antioxidative status in development of the consequences of biological action under low dose and low intensity irradiation

The scale and direction of changes of a number of biophysical, biochemical and physiological parameters in SHK mice (male) tissues were studied depending on their initial values for mice control groups within 1 day after low intensity gamma-irradiation (15 cGy). The reciprocal dependences between the scales of the lipid antioxidative activity (AOA) in brain or the spleen mass changes and their values for mice control groups were found. The external dependences were revealed between the amounts of lipid peroxidation secondary products in spleen, liver and blood plasma of the control mice and a scale of their change after irradiation. The most substantial changes of this parameter were observed in blood plasma and the changes of the phospholipid content within the total lipid composition were found in spleen and blood erythrocytes of the irradiated mice, that is in the lipids of tissues, which had the lowest level of AOA for mice control groups. The experimental data obtained indicate that the initial antioxidant status of animal tissues plays the important role for the development of consequences of the biological action under low dose and low intensity irradiation.     

Changes in functional activity of the synthetic apparatus of rat thymocytes under acute and chronic gamma-irradiation

The changes in functional activity of rat thymocyte synthetic apparatus (synthetic activity) under acute (7.5 Gy) and continuous (dose rates 14.4 and 0.43 cGy/day) gamma-irradiation were studied by the fluorescent microspectral analysis. It has been shown that after the acute irradiation the changes in synthetic activity occurred in three main stages. The stages reflect the depression and activation of synthetic processes that is due to interphase and reproductive cell death and urgent recovery of thymus cellularity and secondary repopulating. Under continuous irradiation with a dose rate 14.4 cGy/day in long-term period both the decrease of thymocyte synthetic activity (in most animals) and activation (in the animals with pronounced symptoms of radiation damage) were observed. This reflects the depression processes in immune system and augmentation of immunoreactivity due to mass antigen influence of transformed cells and infectious agents on thymocytes. Under low dose ionizing irradiation (dose rate 0.43 cGy/day) the undulating changes in synthetic processes in thymus cells were observed. This depends on the recurrence of depression and recovery processes in the blood-forming tissue.     

Changes in superoxide production rate and in superoxide dismutase and glutathione peroxidase activities in subcellular organelles in mouse liver under exposure to low doses of low-intensity radiation

The functioning of the antioxidant system in mouse liver at increased stationary concentration of active oxygen species induced by whole-body chronic exposure of mice to gamma-irradiation (137Cs, 0.6 cGy/day, 9 days) was studied. Synchronous changes (growth with an extreme) in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are found that may be considered as evidence in favor of maintenance of regulatory links in the antioxidant system of liver. The superoxide production rate in microsomes and nuclei also changed with an extreme with the rise in accumulated radiation dose. In microsomes the superoxide production rate reached a maximum at lower doses than the activity of Cu,Zn-SOD did. In nuclei the increase in superoxide production rate was not compensated by the rise in Cu,Zn-SOD activity within the studied dose range. The findings indicate some imbalance between production and consumption of superoxide radicals in microsomes and nuclei; in mitochondria these processes are balanced, leading to more resistance to low-dose irradiation.     

The low dose and low dose rate cytogenetic effects induced by gamma-radiation in human blood lymphocytes in vitro. II. the results of cytogenetic study

The yield of chromosome aberrations induced by gamma-radiation of 60Co in human blood lymphocytes in vitro at low doses (30 divided by 600 mGy) and low dose rates (0.70, 5.05, 59.2 mGy/min) was investigated. It was found that the observed level of chromosomal aberrations induced by gamma-irradiation was unaffected by the value of the dose rate when using constant dose rate and obtaining different doses by altering the exposure time. However, a relatively enhanced level of chromatid aberrations was found at 5.05 and 59.2 mGy/min dose rates in the dose range less than 250 mGy. We have found that the observed level of the sum of chromosomal aberrations induced by gamma-irradiation at doses less than 250 mGy and a dose rate of 59.2 mGy/min was essentially larger compared with the level extrapolated from high doses (above 300 mGy) using a linear-quadratic dose curve. This complied with our previous finding in 1976, 1977 when the enhanced level of dicentrics was only found at a high dose rate approximately 500 mGy/min. Such a non-linear cytogenetic effect does not manifest itself statistically significantly at dose rates of 0.70 and 5.05 mGy/min for the sum of chromosomal aberrations and does not manifest itself at all for dicentrics at all the examined dose rates.     

Evaluation of the genetic effects of 238Pu incorporated into mice

The genetic effects of 238Pu incorporated into male mice were estimated by several tests. The activity of the administered 238Pu nitrate varied from 7 to 1850 Bq/g of body weight. The average alpha-radiation dose absorbed in the testes ranged from 2 to 96 cGy, with a dose rate of 0.004-1 cGy/day. alpha-Radiation from 238Pu was shown to induce dominant lethal mutations (DLM) and reciprocal translocation (RT), chromosomal fragmentation and formation of abnormal sperm heads (ASH). The effect does not depend on the average alpha-radiation dose absorbed in the testis. The relative genetic efficiency of alpha-radiation, as compared with that of chronic alpha-radiation for the indices under study, was about 10-20.     

Relative biological effectiveness and dose rate effect of tritiated water on chromosomes in human lymphocytes and bone marrow cells

Tritriated water (HTO) is a major toxic effluent from the nuclear power industry, that is released into the environment in large quantities. The low dose radiation effect and dose rate effect of HTO on human lymphocytes and bone marrow cells have not been well studied. The present study was therefore undertaken to investigate the HTO dose-response relationship for chromosomal aberrations in human lymphocytes and bone marrow cells at low in vitro radiation doses ranging from 0.1 to 1 Gy. Lymphocytes (G₀ stage) and bone marrow cells were incubated for 10–150 min with HTO at a dose rate of 2cGy/min (555 MBq/ml). The relative biological effectiveness (RBE) of HTO was calculated with respect to ₆₀Co γ-rays for the induction of dicentric and centric ring chromosomes at low radiation doses. The RBE value for HTO β-rays relative to ⁶⁰Co γ-rays was 2.7 for lymphocytes and 3.1 for chromatid aberrations in bone marrow cells. Lymphocytes were also chronically exposed to HTO for 6.7–80 h at dose rates of 0.5 cGy/min (138.5 MBq/ml) and 0.02 cGy/min (5.6 MBq/ml). There was a 71.5% decrease in the yield of dicentrics and centric rings at the dose rate of 0.02 cGy/min, indicating a clear dose rate effect of HTO. The RBE value for HTO relative to ¹³⁷Cs γ-rays was 2.0 at a dose rate of 0.02 cGy/min, suggesting that low HTO dose rates produce no increase of the RBE values and that the values may be constant between 2 and 3 within these dose rates. These results should prove useful in assessment of the health risk for humans exposed to low levels of HTO.     

Genetic efficacy of low doses of ionizing radiation in chronically-irradiated small mammals

Earlier we have established the genetic effects of low dose chronic irradiation in bank vole (somatic and germ cells, embryos), in pond carp (fertilized eggs, embryos, fry) and in laboratory mice (somatic and germ cells) in the range of doses from near-background to 10 cGy. These low dose effects observed in mammals and fish are not expected from extrapolation of high dose experiments. For understanding reasons this discrepancy the comparative analysis of genetic efficiency of low dose chronic irradiation and the higher doses of acute irradiation was carried out with natural populations of bank vole which inhabited the two sites differing in ground of radionuclide deposition. For comparing efficiency the linear regression model of dose-effect curve was used. Dose-effect equations were obtained for animals from two chronically irradiated bank vole populations. The mean population absorbed doses were in the range 0.04-0.68 cGy, the main part of absorbed doses consisted of external radiation of animals exposed to 137Cs gamma-rays. Dose-effect equations for acute irradiation to 137Cs gamma-rays (10-100 cGy) were determined for the same populations. Comparison of genetic efficiency was made by extrapolation, using regression coefficient beta and doubling dose estimation. For chronic exposure the doubling doses calculated from low-dose experiments are 0.1-2 cGy and the doubling doses determined from high-dose experiments are in the range of 5-20 cGy. Our hypothesis that the doubling dose estimate is calculated in higher-dose ionizing radiation experiments should be much higher than the deduced from the low dose line regression equation was verified. The doubling dose estimates for somatic cells of bank vole and those for germ cells of laboratory mice are in close agreement. The radiosensitivity of bank vole chromosomes were shown is practically the same as that for human lymphocytes since doubling dose estimates for acute irradiation close to each other. For low LET radiation a higher genetic efficiency of chronic low doses in comparison with the higher doses of acute gamma-irradiation (137Cs source) was proved by three methods.     

Morphofunctional state of the rat male reproductive system after chronic low intensity irradiation at a dose of 1.0 Gy

It was studied the morphofunctional state of rat male reproductive system after chronically exposure to low intensive gamma-irradiation in early ontogenesis. After radiation with a total dose of 1.0 Gy it was revealed the decrease of the testes and epididymis weight, dysbalance in the ratio of different spermatogenic cells, changes in nucleic acid content and discoordination of bioenergetic metabolism in testes. Disturbance in rat male reproductive system retained in remote period (180 days after irradiation).     

Effects of prolonged low-intensity irradiation on organ weight of the male rat reproductive system

The effects of prolonged irradiation at accumulated doses from 0.5 to 6.0 Gy (dose rate 3.03 cGy/day) on reproductive organs' weight (testes, epididymises, seminal vesicles, prostate) of male rats starting from the early ontogenetic period were studied. On the first day after the irradiation with 1.0 Gy dose a significant loss of the weight in testes and epididymises was revealed. This leaded to the marked atrophy of the organs with the increase of the radiation dose. Long-term restoration of the weight of testes and epididimyses was registered. It was not completed during three months after radiation exposure at 2.0 Gy and higher doses for epididimyses and 4.0-6.0 Gy for testes. The respective changes in the seminal vesicles and prostate weight were less pronounced and had more complicated character. However in the distant period (30-90 days of postreatment) after exposure to 2.0 Gy these parameters were noticeably decreased.     

Recruitment of cells in the small intestine into rapid cell cycle by small doses of external gamma or internal beta-radiation

Epithelial cell recruitment was examined in mouse ileum after external gamma-irradiation (50 cGy) or internal beta-irradiation (0.148 MBq/g of [3H]thymidine), using the per cent-labelled-mitoses method and by analysing the distribution of mitotic cells in the crypts. In the presumptive stem cell zone at the lower cell positions of the crypt, the slowly cycling cells decreased their cell cycle 6 or 12 hours after a dose of 50 cGy. In the higher cell positions, a slight shortening of the cell cycle was also observed. After administration of a high dose of [3H]thymidine, dormant (G0) cells also entered the cell cycle in the lower cell positions. The results suggest that stem cells in the crypt may react to irradiation in two ways: first, by shortening the cell cycle in cycling cells; secondly, by an entry into the cell cycle by other dormant cells. There was destruction of some cycling stem cells before any recruitment. The data support the idea that the stem cell population in the crypt is heterogeneous.     

Transformation of C3H 10T1/2 cells with 4.3 MeV alpha particles at low doses: effects of single and fractionated doses.

Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV alpha particles LET = 101 keV/microns. The source of alpha particles was 244Cm and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mitotic yield decreased markedly with the total dose delivered, and it was as low as 50% of the control value after 4.2 cGy and 20% after 14 cGy with both fractionation schemes.     

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1). The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5-7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.     

The effects of low doses of low-level gamma-radiation and phenozan injection on structural characteristics of mice spleen DNA

It is well known that AKR mice with spontaneous leucosis are more sensitive to ionizing irradiation as compared to normal F1 (CBA x C57BL) mice. A study on changes of the structural characteristics of spleen DNA and level of protein p53 in the blood serum under the action of low-level gamma-irradiation in a dose of 1.2 cGy and injections of 10(-14) or 10(-4) mol/kg phenozan was performed. The changes in the structural characteristics of DNA (the adsorption on nitrocellulose filters and number of double-strand breaks) and p53 content were observed for each line of mice under gamma-irradiation and each phenozan concentration. Both factors showed long-time post-effects, and structural changes in AKR DNA were consistent with the life span of these mice. Phenozan in the above doses has abolished the induction of double-strand breaks in case of irradiation of F1 mice in a dose of 1.2 cGy and showed long-time post-irradiation effect. These facts suggest a radioprotection property of phenozan.     

Response of a brachytherapy model using 125I in a murine tumor system

The effects of low-dose-rate irradiation (brachytherapy) were investigated in vivo using a murine mammary adenocarcinoma (MTG-B) growing in the flank of C3H mice. For local tumor irradiations, a noninvasive cap was devised to cover the tumor and house three 125I seeds (average apparent activity 5.2 mCi each) located at 120 degree intervals around the circumference of the hemispherical cap (13 mm i.d.). Mice were secured during treatment in a tube allowing limited mobility while restricting access to the seeds. Tumors were exposed to a series of dose rates ranging from 14-40 cGy/h, and the total dose over the treatment interval (48 or 72 h) ranged from 830 to 2378 cGy. A total of nine experiments were conducted using the caps over a 10-week interval. In each experiment three groups (irradiated tumors, sham controls, and untreated controls) were analyzed, each containing 8-15 mice (N = 34, untreated control; N = 46, sham control; N = 91, brachytherapy irradiation). The brachytherapy results are compared to the effects of external beam irradiation in the same tumor system. A linear relationship was observed between the total radiation dose and doubling volume growth delay (GDDV) or treatment volume growth delay (GDTV) for the brachytherapy and external beam irradiation. The slopes of the dose-response curves are steeper for the acute dose (517 cGy/min) external beam irradiation (0.0072 day/cGy, GDDV; 0.00695 day/cGy, GDTV) than for the brachytherapy (0.0050 day/cGy, GDDV; 0.0057 day/cGy, GDTV) using both GDTV and GDDV end points. Comparison of the tumor volume regrowth slopes indicates that the tumor bed effect is larger for external beam irradiation than for brachytherapy, suggesting that the tumor bed effect may be dose-rate dependent.     

Biological effects of phytoecdysteroids and chronic low-dose irradiation

The influence of serpistene in dose of 5 and 50 mg/kg on chronic low-dose gamma-irradiation (22.6 cGy) effects on cytogenetic (abnormal sperm cell, marrow bone micronucleus) and function and morphology (thyroid and adrenal glands) parameters of mice was estimated. The serpistene modifies effects of gamma-irradiation depends on the administration regime and a dose of the substance. The most expressive radioprotective effect on endocrine organs after serpistene prophylactic administration was found. The prophylactic dose was 5 mg/kg for adrenal gland and both doses--for thyroid gland. The most expressive radioprotective effect on marrow bone cells after serpistene therapeutic administration in a dose of 5 mg/kg was found. The most expressive antimutagenic effect on somatic and germinal cells of prophylactic and therapeutic administration in a dose of 50 mg/kg was found.     

Genetic effects in the liquidators of consequences of Chernobyl Nuclear Power Plant accident

The purpose of the present research was the estimation of probable genetic consequences at the liquidators of the consequences of Chernobyl accident in 1986-1987. The research is made on two groups of the liquidators. The first group included the liquidators taking place on the account in the branch register and working now at the enterprises of a nuclear industry. The second group included 902 liquidators of consequences of Chernobyl accident in 1986 constantly living in the Ryazan area and which are taking place on permanent observation the account in regional hospital. For an estimation of probable genetic effects analyzed the data on frequency and outcomes pregnancy of the wives of the liquidators, on condition and on diseases of newborn, on switching intrauterine development defects (IDD). The analysis carried out depending on dozes of an irradiation: up to 5 cGy; 5-10 cGy and 10-25 cGy. Received materials testify, that at the liquidators, at a doze of an external irradiation 10-25 cGy, the determined effects--period long sterility, kept at a part them till 3 years come to light. The set of the received data, such as depending from the dose increase of frequency of spontaneous abortions and of inherent defects of development of newborn, the increase of frequency diseases of newborn and share newborn with low weight, allows to make a conclusion about an induction of genetic effects in sexual cells of the liquidators of consequences of Chernobyl accident at dozes of an external irradiation more than 10 cGy. Taking into account high biological efficiency of alpha-radiation (K = 20), and of beta-radiation (K = 2-4), the equivalent effective doze male gonads (testes) in 3-5 times is higher, than estimated only from external gamma-radiation.