The dopamine system in rat brain areas in the early period following irradiation with superhigh doses]

In studying the main indices that characterize the neurochemical system of biosynthesis and degradation of a dopamine neuromediator, tyrosine hydroxylase-dopamine-monoamine oxidase, in different brain regions 5-6 min, 1 and 18 h after whole-body irradiation with high energy electrons (100 Gy) the authors have revealed a 25-40% inhibition of tyrosine hydroxylase and monoamine oxidase activity, and a 40% increase in the dopamine content of basal ganglia of the brain that control behavioural reactions of the organism. The neurochemical disturbances revealed are involved in the mechanisms of early transient incapacity after irradiation with superhigh doses.     

Mechanisms of radiation impairment of DNA biosynthesis. Separation, partial purification, characteristics of and changes in DNA polymerase alpha and beta activities of rat bone marrow at early stages after gamma irradiation and comparison with the status of repair and replication biosynthesis of DNA

Activity of alpha and beta DNA-polymerases in nuclei and cytosol and also replicative and repair biosynthesis of DNA in the bone marrow were determined during the first hours following whole-body gamma-irradiation of rats with a dose of 6 Gy. There was a pronounced and reliable correlation between postirradiation changes in activities of both DNA-polymerases in nuclei and also semiconservative and repair biosynthesis of DNA in bone marrow cells. The results were obtained by the method of separation and partial purification of alpha and beta polymerase the most important characteristics of which are presented.     

Mechanisms of the radiation-induced disorder of DNA synthesis. The correlation of biosynthesis, DNA repair and DNA polymerase alpha and beta activity in the bone marrow of rats exposed to gamma quanta and fast neutrons

A study was made of DNA biosynthesis and repair and alpha- and beta-DNA-polymerase activity in rat bone marrow during the first 24 hours following whole-body irradiation with gamma-quanta and fast neutrons (up to 6 Gy). There was a correlation between the post-irradiation inhibition of DNA biosynthesis, a decrease in DNA-polymerase activity and template reparability. The data obtained permitted to consider the radiation-induced disturbance of DNA biosynthesis and the change in beta-polymerase activity as one of the possible mechanisms of formation of high relative biological effectiveness of neutrons.     

Signal function of the reactive oxygen species in regulatory networks of the cell reaction to damaging effects: contribution of radiosensitivity and genome instability

Reactive oxygen species (ROS) have a few possible effects, such as metabolic (participation in regulation of protein functions), damaging (oxidative damage to proteins, lipids and nucleic acids) and signal; the latter is reviewed in the article. Superoxide anion-radical (O2-.), hydroperoxide (HO2) and nitroxide (NO) are capable to act as signal substances in the cell regulatory network, which determines a mode of cell response to disturbance: proliferation pace, a course of differentiation or a start of the apoptosis program. A role of ROS in the reaction network is reviewed: importance of their content in a cell; ROS-bound signal pathways, which trigger the programs of cell reactions to stimuli; initiations of the regulatory network, which determine a content of ROS in a cell; ROS reactions with network components, which influence its functioning. A significance of the ROS-bound segment of the network, which realizes regulatory signals of the damage, in formation of radiobiological effect is estimated. The data obtained by the authors are submitted; the prospects of studing substances (such as phenozan etc.), which can actively influence redox processes, as means of modification of radiation-induced genome instability and prevention of oncogenic transformation are considered.     

Interrelations between the content of reactive oxygen species and the state of DNA structure in bone marrow cells of mice after whole body gamma-irradiation

The aim of the research is a further analysis of a problem concerning two (regulatory and damaging) functions of reactive oxygen species (ROS) in viability of organism cells under acute exposure to ionizing radiation. For this purpose the ROS content and the state of DNA structure in bone marrow cells of male CBA and SHK mice have been studied in dynamics, from 15 minutes up to 185 day after acute exposure to a sublethal dose (1.5 Gy) of ionizing radiation. The analysis of dependencies between these parameters in the norm, immediately after irradiation and in later cell descendants showed the direct correlation between the ROS content and the DNA nativity in the norm; 185 days after irradiation the correlation disappeared. It was suggested that the correlation occurred in the norm indicates participation of the ROS (as a sensory link) in a system of reactions (under the control of the corresponding genetic program), that ensure the DNA structure and, ultimately, the genome stability. The loss of such connection after acute exposure to ionizing radiation indicates actuation of another module of reactions sustaining stability of cellular genome in new conditions, without regulatory participation of ROS, that can promote or demonstrate the development of radiation-induced genome instability.     

Processing of viral envelope glycoprotein by the endomannosidase pathway: evaluation of host cell specificity

Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide processing which through its capacity to cleave the internal linkage between the glucose-substituted mannose and the remainder of the polymannose carbohydrate unit can provide an alternate pathway for achieving deglucosylation and thereby make possible the continued formation of complex oligosaccharides during a glucosidase blockade. In view of the important role which has been attributed to glucose on nascent glycoproteins as a regulator of a number of biological events, we chose to further define the in vivo action of endomannosidase by focusing on the well characterized VSV envelope glycoprotein (G protein) which can be formed by the large array of cell lines susceptible to infection by this pathogen. Through an assessment of the extent to which the G protein was converted to an endo-beta-N- acetylglucosaminidase (endo H)-resistant form during a castanospermine imposed glucosidase blockade, we found that utilization of the endomannosidase-mediated deglucosylation route was clearly host cell specific, ranging from greater than 90% in HepG2 and PtK1 cells to complete absence in CHO, MDCK, and MDBK cells, with intermediate values in BHK, BW5147.3, LLC-PK1, BRL, and NRK cell lines. In some of the latter group the electrophoretic pattern after endo H treatment suggested that only one of the two N-linked oligosaccharides of the G protein was processed by endomannosidase. In the presence of the specific endomannosidase inhibitor, Glcalpha1-->3(1- deoxy)mannojirimycin, the conversion of the G protein into an endo H- resistant form was completely arrested. While the lack of G protein processing by CHO cells was consistent with the absence of in vitro measured endomannosidase activity in this cell line, the failure of MDBK and MDCK cells to convert the G protein into an endo H-resistant form was surprising since these cell lines have substantial levels of the enzyme. Similarly, we observed that influenza virus hemagglutinin was not processed in castanospermine-treated MDCK cells. Our findings suggest that studies which rely on glucosidase inhibition to explore the function of glucose in controlling such critical biological phenomena as intracellular movement or quality control should be carried out in cell lines in which the glycoprotein under study is not a substrate for endomannosidase action.      

Influence of language and ancestry on genetic structure of contiguous populations: A microsatellite based study on populations of Orissa

Background

Although cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the severity of disease is highly variable indicating the influence of modifier genes. The intestines of Cftr deficient mice (CF mice: Cftr ^tm1Unc ) are prone to obstruction by excessive mucus accumulation and are used as a model of meconium ileus and distal intestinal obstruction syndrome. This phenotype is strongly dependent on the genetic background of the mice. On the C57Bl/6 background, the majority of CF mice cannot survive on solid mouse chow, have inflammation of the small intestine, and are about 30% smaller than wild type littermates. In this work potential modifier loci of the CF intestinal phenotype were identified.

Results

CF mice on a mixed genetic background (95% C57Bl/6 and 5% 129Sv) were compared to CF mice congenic on the C57Bl/6 background for several parameters of the intestinal CF phenotype. CF mice on the mixed background exhibit significantly greater survival when fed dry mouse chow, have reduced intestinal inflammation as measured by quantitative RT-PCR for marker genes, have near normal body weight gain, and have reduced mucus accumulation in the intestinal crypts. There was an indication of a gender effect for body weight gain: males did not show a significant improvement at 4 weeks of age, but were of normal weight at 8 weeks, while females showed improvement at both 4 and 8 weeks. By a preliminary genome-wide PCR allele scanning, three regions were found to be potentially associated with the milder phenotype. One on chr.1, defined by marker D1Mit36, one on chr. 9 defined by marker D9Mit90, and one on chr. 10, defined by marker D10Mit14.

Conclusion

Potential modifier regions were found that have a positive impact on the inflammatory phenotype of the CF mouse small intestine and animal survival. Identification of polymorphisms in specific genes in these regions should provide important new information about genetic modifiers of the CF intestinal phenotype.     

The individual prognosis of the gravity and of the outcome of acute radiation disease based on immunological indexes

The information significance of the immunological indexes for the prognosis of gravity of course and of outcome of an acute radiation disease for the people after the exposure of ionizing radiation in clinically significant doses is studied. The value of indexes of the C-reactive protein contents, of the complement contents and of the titer of haemagglutinins in serum of a blood of 147 patients damaged at Chernobyl NPP accident as a result of external radiation gamma-exposure in combination with internal irradiation from the incorporation in an organism predominantly beta-emitting radionuclides were compared to the weight of acute radiation disease and its outcome (survival or loss). Was determined, that indexes of the contents of C-reactive protein in a peripheral blood during primary reactions on the irradiation (1-2 day after irradiation) and in latent period of disease (3-9 day after irradiation), and also titer of a complement on 3-9 day after irradiation can serve a source of information for the prognosis of probable gravity of a radiation injury and its outcome at irradiation of the man in clinically significant doses.