The regulation of the oxidative processes in the tissues of Muridae like rodents caught in the Chernobyl accident zone

The results of the investigations of the radioactive contamination consequences on the lipid peroxidation (LPO) processes in organs and tissues of wild rodents which were caught in the Chernobyl NPP accident 30-km zone during 1986-1993 are generalized. The behaviors of the technogenic contamination effect on dynamic of changes of the LPO physico-chemical regulatory system parameters and the generalized parameters of the phospholipid composition in organs of the different radioresistance wild rodents are revealed in dependence on the radioactive contamination level and the duration of the radiation factor exposure. Different sensitivity of the LPO regulatory system parameters in wild rodent tissues to the radioactive contamination of their environment and the unequal ability to normalization of the antioxidant status and the energy exchange in tissues result in the change of the scale and character of interrelations between the reciprocal parameters in norm and have an influence on the development of qualitatively new subpopulations of wild rodents due to the transition of the cell regulatory system to the another level of the function.     

The phospholipid composition of the liver in root voles living under different radioecological conditions

The effect of the increased natural radiation background (within some areas in Komi Republic) and man-caused radioactive contamination in the Chernobyl NPP accident zone on the composition of liver phospholipids in Microtus oeconomus inhabiting these areas was studied. The significant changes in the liver lipid composition in rodents inhabiting both the Chernobyl accident zone and the areas with the increased natural radiation background were found. The maximal changes in the liver phospholipid composition were revealed during the first year after the accident. The reverse dependence between the phosphatidyl choline/phosphatidyl ethanolamine ratio and the ratio between the sum of more readily oxidizable phospholipids and the sum of more poorly oxidizable ones was found. However, the slope of corresponding curves significantly depends on the radioactive state in the area of the population inhabitance. The conclusion about high sensitivity of the lipid composition of hepatocytes in Microtus oeconomus both to the impact of the man-caused radioactive contamination and the increased level of the natural radioactivity was drawn.     

A new approach to assessment of biological consequences of exposure to low-dose radiation

A high sensitivity of characteristics of the lipid metabolism in erythrocytes to exposure to low doses of gamma- and X-rays was found; the changes in lipid peroxidation (LPO) of blood components were persistent, which substantially influenced the development of biological consequences of low doses of radiation. The effect of low doses of radiation on the interrelation between the LPO intensity in blood plasma and the lymphocyte DNA structural integrity or the cell-free DNA content in animal blood plasma was found. Different sensitivity of the examined parameters (neither normalization nor linear dependence on a dose rate was found) implies the transition of the LPO regulatory system to another level of functioning due to scale changes of interrelations between the examined parameters under influence of low doses of radiation. These findings make possible to assess biological consequences of radiation factor for animal groups by the scale changes of interrelations between the examined characteristics in blood plasma.     

Monitoring of tundra vole (Microtus oeconomus Pall.) population inhabiting areas with increased radiation background

The data of complex examinations of morphophysiological state of Tundra vole (Microtus oeconomus Pall.), the lipid peroxidation (LPO) processes and the energy exchange in their organs, the cytogenetic analysis of marrow cells and the process of multiplication in populations inhabiting areas with increased natural radiation background more 50 years are generalized. The data obtained support the existence of qualitative differences of Tundra vole subpopulations inhabiting control and radioactive nuclide contaminating areas. They allow to suppose that the process of adaptation to chronic low intensity radiation effect of Tundra vole in natural conditions involves the transition of the LPO and another regulatory systems to different level of function and is directed on population survival and homeostasis maintenance in changing radioecological conditions.     

Dependence of response reaction of root voles to low-intensity irradiation on the initial state of the tissue antioxidant system

There has been studied the response of antioxidant (AO) reaction of the tissue system of the root voles Microtus oeconomus Pall. whose parents belonged to the populations long inhabiting the Republic Komi regions with different degrees of radioactive contamination on an additional radiation action at low doses. Differences have been revealed in the phospholipid content, activities of AO defense, intensities of processes of lipid peroxidation (LPO) in tissues of the vole offspring caught in the control and contaminated regions. It has been revealed that direction and degree of changes in the offspring tissues after the additional action are determined by the parameter value in the non-irradiated animal group. Intensity of the LPO processes in liver and brain was leveled after the long low-intensity irradiation. The obtained data and analysis of literature indicate that at predicting effects of chronic action of low doses of a damaging factor both in experiment and in the natural habitation, it is necessary to take into account initial characteristics of biological objects.     

Effect of oxidative processes in lipids on the formation of the biological response during combined exposure to X-rays and chemical agents

It shown that the preliminary administration of the low toxic surfactant (Tween 80) and of acetone at low doses increases the action of the acute X-rays with sublethal and lethal doses on the living organisms. The absence of the linear dependence between the biochemical changes of the lipid peroxidation (LPO) regulatory system and initial levels of parameters of this system was found. The gain of the effect of the action on the LPO intensity in tissues and the changes in the scale and direction of the interrelation between the antioxidative status parameters in murine liver under combined exposure of the damaging factors of the chemical and physical nature was found.     

Parameters of peroxidation and proteolysis in the organism of the liquidators of Chernobyl accident consequences

The specificity of lung irradiation caused by ionizing radiation is influence on mucous membranes of respiratory ways, alveolar epithelium and capillaries of a small circle of the blood circulation. Under diseases of bronchus-lung system the lipid peroxidation (LPO) processes activation is observed. The radiating influence strengthening effect. In results in imbalance aggravation in system "LPO-antioxidants", and long expressing of LPO intensification is the important mechanism of the inflammation chronization. The sharp increase of proteolytic activity and inhibitor activity decrease is found out in the patients-liquidators. Noticed imbalance results in the further change of permeability of membranes and correlates with an index of endoscopy inflammation changes and index of irreversible changes in lung tissue. Thus, the direct connection between LPO intensity and imbalance degree of proteinase-inhibitor system of blood at the patients with chronic bronchitic taking part in Chernobyl accident liquidation is revealed.     

Results of experimental radiobiological studies made within the 10-kilometer zone of the Chernobyl AES accident]

A study was made of the effect of high radioactive contamination on the animal organism (C57BL/6 mice) and HeLa cell culture within the ten-kilometer zone of the Chernobyl A.P.S. accident. The total radiation dose, as calculated by a gamma-component, was 0.09 to 2 Gy. A long-term exposure of mice within the zone (cumulative dose of 1.8 to 2 Gy) caused a significant decrease in bone marrow stem potencies and changes in the brain vascular system; subsequent acute exposure of animals increased interferon titres in the serum to a much greater extent than a single acute exposure did. As to HeLa cells, irradiation there of with doses of 0.09 to 0.4 Gy during 15-20 postirradiation generations caused a decrease in the proliferative activity, an emergence of cells with micronuclei and of giant cells, and remote cell death.     

Analysis of microsatellite DNA in rodents from Eastern Urals Radioactive Trace zone and contiguous territories

The variability of four microsatellite loci of rodents, caught from the head part of Eastern Urals Radioactive Trace (EURT), along with the rodents inhabiting contiguous zone with background radiation level and distant reference territory, was analyzed for the first time. Differences in the parameters of genetic diversity between northern red-backed voles from the EURT zone and from the reference population were detected. An increase in some indices of genetic diversity in animals from a contiguous to the EURT zone was found; this is probably associated with animal migration and configuration of the area of pollution. A transfer of radiation-induced effects to the contiguous territories and a decrease in the possibility of fixation of adaptations in a series of generations of mobile rodent species in the area of local radioactive pollution are consequences of migrations. The results of the study make it possible to recommend microsatellite markers for the analysis of radiation-induced effects in rodents as model objects of radioecological monitoring.     

Hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers

A single accidental event such as the fallout released from the Chernobyl reactor in 1986 can expose millions of people to non-natural environmental radiation. Ionizing radiation increases the frequency of germline mutations in experimental studies, but the genetic effects of radiation in humans remain largely undefined. To evaluate the hereditary effects of low radiation doses, we compared the minisatellite mutation rates of 155 children born to Estonian Chernobyl cleanup workers after the accident with those of their siblings born prior to it. All together, 94 de novo paternal minisatellite mutations were found at eight tested loci (52 and 42 mutants among children born after and before the accident, respectively). The minisatellite mutation rate was nonsignificantly increased among children born after the accident (0.042 compared to 0.036, OR 1.33, 95% CI 0.80-2.20). Furthermore, there was some indication of an increased mutation rate among offspring born after the accident to workers who had received doses of 20 cSv or above compared with their siblings born before the accident (OR 3.0, 95% CI 0.97-9.30). The mutation rate was not associated with the father's age (OR 1.04, 95% CI 0.94-1.15) or the sex of the child (OR 0.95, 95% CI 0.50-1.79). Our results are consistent with both no effect of radiation on minisatellite mutations and a slight increase at dose levels exceeding 20 cSv.     

Late occurring lesions in the skin of rats after repeated doses of X-rays

Late radiation damage, characterized by atrophy and necrosis in the skin and subcutaneous tissues, has been demonstrated in both the tail and feet of rats. The incidence of necrosis increased with total dose. These total doses, in the range 72-144 Gy, were given as 4-8 treatments of 18 Gy, each dose separated from the next by an interval of 28 days. This treatment protocol minimized acute epithelial skin reactions. The same regime applied to the skin on the back of rats resulted in a very severe acute reaction occurring after the second to fifth dose of 18 Gy. This was surprising since back skin, like tail skin, is less sensitive to large single doses of radiation than that of the foot. The late radiation reaction in the foot and tail of rats are compared and contrasted with other attempts to assess late effects in rodent skin and with late changes seen in pig skin.     

Phospholipid composition of blood erythrocytes of tundra voles (<Emphasis Type="Italic">Microtus oeconomus</Emphasis> Pall.) inhabiting under different radioecological conditions

Phospholipid composition has been studied in blood erythrocytes of tundra voles Microtus oeconomus inhabiting territories with normal and increased levels of natural radioactivity in different phases of the population cycle. It has been shown that rearrangement in the lipid component of blood erythrocyte membranes of tundra voles from radioactively polluted areas are associated with intensification of the lipid peroxidation (LPO) processes and are similar to those observed at the organism natural aging. It has been noted that the capability for peroxide oxidation in erythrocyte lipids is one of the most sensitive stages of the LPO processes to action of the low-intensity radiation in the natural habitat of animals. The change of the populational cycle phases, which is accompanied by hormonal rearrangements in the animal body, produces an essential effect on the degree of expression of the radiation-induced changes of the studied parameters.     

The effects of UV radiation on the visual system of the crab Neohelice granulata: a protective role of melatonin

The first and main target-structure of ultraviolet (UV) radiation in animals is the body surface, including the skin and eyes. Here, we investigated cell damage in the visual system of the crab Neohelice granulata acclimated to constant light and exposed to UVA or UVB at 12:00 h for 30 min. The reactive oxygen species (ROS) production, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO) damage, catalase (CAT) activity, and the melatonin immunohistochemical reactivity in the eyestalks were evaluated. The animals that received melatonin and were exposed to UVA and UVB radiation showed a decreased ROS concentration (p < 0.05).The ACAP test showed a decrease (p < 0.05) in their values when the animals received 2 pmol/crab of melatonin (physiological dose) before the exposure to UVA radiation. The animals exposed to UVB radiation after receiving the same dose of melatonin showed an increase (p < 0.05) in the ACAP test compared with the animals exposed to UVB radiation after receiving only crab physiological saline. The CAT activity increased (p < 0.05) in the animals that received melatonin and were exposed to UVA and UVB radiation. Animals exposed to UVA and UVB displayed an increase (p < 0.05) in the LPO levels, whereas animals treated with melatonin showed lower (p < 0.05) LPO levels when irradiated. The results indicate that the specific oxidative parameters altered by UV radiation can be modulated by a physiological dose of melatonin. Moreover, the melatonin regularly produced by virtually all eyestalk cells suggests that it may function to modulate the noxious effects of radiation, at least in the crab N. granulata.     

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.     

Glutathione-deficient state of nervous tissues in starved animals intensifies lipid peroxidation and oxidation of protein SH-groups

The levels of the lipid peroxidation products (LPO), different forms of protein SH-groups and their oxidation rate in the homogenates of the mesencephalon, hypothalamus and sensorymotor cortex of normal and GSH-deficient rats under 3-day food starvation were studied. It was shown, that the basic level of LPO products--lipid hydroperoxides and malonic dialdehyde (MDA) in hypothalamus and sensorymotor cortex of normal animals are by 20-30% (p < 0.05) higher and reduced glutathione (GSH) content is 2 times higher, than these values in mesencephalon. Under 3 day starvation of normal animals activation of the LPO observed only in the hypothalamus and sensorymotor cortex, whereas under 3 day starvation of the GSH-deficient rats formed by the intraparenteraly injection of diethylmaleate in a dose of 2.5 mmol/kg of body weight in all investigated structures the lipid hydroperoxides and MDA increased many times (2-3 times), the content of the surface and masked protein SH-groups decreased and essentially increased the oxidation rate of these functional groups. It was proposed that GSH and its enzymes participate in the LPO regulation and protection of protein SH-groups from oxidative damage at this event the intensity of this prosesse depends on structural and functional organization of nervous tissues.     

The parameters of antioxidant status of tissues in the offspring of tundra vole (Microtus oeconomus Pall.) inhabiting areas with increased natural radioactivity

The parameters of the lipid peroxidation regulatory system (the antioxidative and antiperoxidant activities, the peroxide content, the lipid peroxidation intensity) in the tissues and the activities of the antioxidative defence enzymes (the peroxidase activity in blood, the superoxide dismutase activity in the blood erythrocytes) are studied in progeny of tundra vole which are reproduced from parent inhabiting areas with different radioecological environment during a long time. The progeny had the preservation of the changed antioxidant status. The scale of the changing of the investigating parameters depend on the state of radionucleoids contamination of areas where tundra voles are caught, sex of rodents, the content of antioxidants in lipids of tissues of parents.     

The Chernobyl fallout in Salzburg/Austria and its effect on blood chromosomes

The radioactive fallout of the Chernobyl accident caused an increase in radiation dose of 20 to 110 per cent over the normal environmental burden to the inhabitans of Salzburg City in Austria (in a distance of about 1300 km from the accident). The structural chromosome aberration in the lymphocytes of the peripheral blood of 15 test-persons have been investigated one year after the accident. From two of these we know also the aberration frequencies before the accident which were significantly lower. The results from all test persons were pooled according to their Cs137 and Cs134 content, measured by whole body counter. Their mean additional blood doses from the incorporated caesium plus the external fallout radiation were 0.23, 0.36 and 0.55 mGy/yr. The aberration frequencies increased with dose. The slope of the best straight-line through the points was 2.0 +/- 0.7 total chromosome type aberrations in 100 metaphases per mGy/yr. This result fits in well with former investigations of persons with individually calculated radiation burden from the environment. The sharp increase with dose at this low level is not compatible with values extrapolated from high doses. The usual dose assessment based on chromosome aberrations extrapolated from high to low doses is therefore not possible in the range considered in this investigation.     

Dependence of response reaction of root voles to low-intensity irradiation on initial state of the tissue antioxidant system

There has been studied the response of antioxidant (AO) reaction of the tissue system of the root voles Microtus oeconomus Pall., whose parents belonged to the populations long inhabiting the Republic Komi regions with different degrees of radioactive contamination, on an additional irradiation at low doses. Differences have been revealed in the phospholipid content, activity of AO defense, intensity of processes of lipid peroxidation (LPO) in tissues of the offspring of voles caught in the control and contaminated regions. It has been revealed that direction and degree of changes in the offspring tissues after the additional action are determined by the parameter value in the non-irradiated animal group. Intensity of the LPO processes in liver and brain was leveled after the long low-intensity irradiation. The obtained data and analysis of literature indicate that at predicting effects of chronic action of low doses of a damaging factor both in experiment and in the natural habitation, it is necessary to take into account initial characteristics of biological objects.     

Dramatic Increase in Oxidative Stress in Carbon-Irradiated Normal Human Skin Fibroblasts

Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs. X-ray irradiation. Survival curves and radiobiological parameters were calculated. DNA damage was quantified, as were lipid peroxidation (LPO), protein carbonylation and antioxidant enzyme activities. Reduced and oxidized glutathione ratios (GSH/GSSG) were determined. Proinflammatory cytokine secretion in culture supernatants was evaluated. The relative biological effectiveness (RBE) of C-ions vs. X-rays was 4.8 at D₀ (irradiation dose corresponding to a surviving fraction of 37%). Surviving fraction at 2 Gy (SF2) was 71.8% and 7.6% for X-rays and C-ions, respectively. Compared with X-rays, immediate DNA damage was increased less after C-ions, but a late increase was observed at D_10% (irradiation dose corresponding to a surviving fraction of 10%). LPO products and protein carbonyls were only increased 24 hours after C-ions. After X-rays, superoxide dismutase (SOD) activity was strongly increased immediately and on day 14 at D_0% (irradiation dose corresponding to a surviving fraction of around 0%), catalase activity was unchanged and glutathione peroxidase (GPx) activity was increased only on day 14. These activities were decreased after C-ions compared with X-rays. GSH/GSSG was unchanged after X-rays but was decreased immediately after C-ion irradiation before an increase from day 7. Secretion of IL-6 was increased at late times after X-ray irradiation. After C-ion irradiation, IL-6 concentration was increased on day 7 but was lower compared with X-rays at later times. C-ion effects on normal human skin fibroblasts seemed to be harmful in comparison with X-rays as they produce late DNA damage, LPO products and protein carbonyls, and as they decrease antioxidant defences. Mechanisms leading to this discrepancy between the two types of radiation should be investigated.