[Analysis of the mutagenicity of drinking tap water from several Moscow districts and Moscow region].
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Biomedical subjects
Publications and source records attributed to L G Dubinina.
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The mutagenicity of the drinking water from 16 districts of Moscow was investigated by analyzing of chromosome aberrations induced in cells of Crepis capilaris seeds used as a plant test system. Cytogenetic analysis revealed mutagenic activity in drinking water samples from four administrative regions, namely the Biryulevo-Zapadnoe district of Southern region (2.4%), Obruchevskii district of the Southwestern region (1.61%), Severnoe Tushino district of the Northwestern region (1.45%), and Perovo district of the Western region (1.18%). The frequency of chromosome aberrations found was significantly higher than in the spontaneous control (0.37%). Mutagenic activity was not detected in water samples taken from the Moscow oblast and from four open reservoirs.
The present study examines cross-adaptation between alkylating agents and antibiotic mitomycin C (MC). Ethylating and methylating agents induce monoadducts in DNA in the form of ethyl and methyl radicals. MC induces DNA cross-links. In our experiments on cross-adaptation, low concentration of ethylenimine (EI) did not induce an adaptive response following posttreatment with methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (NG) at mutagenic concentration. Pretreatment with low EI concentration and posttreatment with MC did not induce adaptive response to late fixation. Pretreatment with NG at low concentration and subsequent posttreatment with EI at high concentration reduced the yield of chromosomal aberrations (adaptive response), compared to the effect of EI alone. Adaptive response is absent when pre- and posttreatment are performed within phase G1, and the effect of sensibilization is noted in this case. After posttreatment with MC at mutagenic concentration, the adaptive response is expressed in the case of increased cell-cycle duration. Posttreatment with MC at low mutagenic concentration did not lead to any adaptive response following NG pretreatment. In experiments with low MC concentration and posttreatment with high EI concentrations, the adaptive response was observed, whereas in experiments with NG posttreatment, an increased yield of aberrations (the effect of sensibilization) was observed. Thus, in cross-adaptation, inducible repair, i.e., adaptive response, is demonstrated by MC, methylating agent NG, and ethylating agent EI despite differing damage to DNA. This effect is dependent on the character of DNA damage following pretreatment, concentration and character of the mutagen used for posttreatment, and the duration and phase of the cell cycle.
The mutagenic effect induced by mitomycin C (MC) 20 mg/ml in early, middle and late G1-phase of Crepis capillaris seeds was modified by DNA synthesis inhibitors--caffeine 5 mM, hydroxyurea (HU) 5 x 10(-3) M, 1-beta-D-arabinofuranosylcytosine (araC) 1 x 10(-3) M and aphidicolin (APC) 0.5 mg/ml in the DNA post-synthesis phase (G2). It was shown that under the action of MC in early G1 and the inhibitors in the G2 the total number of aberrations for fixations is lower in all the cases than under the action of MC only. The action of MC in the middle phase results in the differential effect of the inhibitors. HU and APC were shown to potentiate the effect induced by MC and ara-C to reduce it. In both cases, caffeine at the dose 5 mM had small effect on DNA damages induced by MC in early and middle G1. Under the action of caffeine and HU in the G2-phase the crosslinks induced by MC in the late G1 result in aberrations of chromosomal type, illegal for the S-dependent mutagenesis. On the whole, the process of mutation formation turned out to be sensibilized. The specificity of mutagenesis under the action of MC suggests the appearance of mutations of the chromosomal type after the DNA synthesis in G2 phase.
The mutagenic effect of mitomycin C (MC) has been shown in the S phase of Crepic capillaris cells. The repair ability of MC-induced DNA lesions proves exceedingly high, due to post-replicative and excision repair processes. In the experiments with MC-pretreatment of Crepic capillaris cells, nonmutagenic concentration of 1 microgram/ml provides inducible repair system--"adaptive response", which considerably decreases the levels of mutagenesis induced by MC at concentrations of 10, 20 and 40 micrograms/ml. Under adaptive response, the action of methyltransferase is possible.
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Air-dry Crepis capillaris seeds, soaked for 14 and 20 hours, were dried to the moisture content of 1,1% with the following gamma-irradiation at a dose of 1500 r. Irradiated seeds were stored in the state of identical moisture for 38 days. The drying of three groups of seeds to moisture content of 1,1% provided their identical initial radiosensitivity. In the course of the storage mutability of treated seeds significantly increased as compared with the yield of mutations in non-stored seeds, and revealed undulating kinetics that involved all types of arising chromosome and chromatid rearrangements. The character of undulating kinetics is due to a correlation between functional state of nucleus (early G1, late G1, S) and water content in seeds.
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