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首页> 外文期刊>Journal of environmental sciences >Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human-hamster hybrid cells
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Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human-hamster hybrid cells

机译:一氧化氮在人仓鼠杂交细胞中对慢性微囊藻毒素-LR暴露的遗传毒性反应中的作用

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Microcystin-LR (MC-LR) is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen (Group 2B) by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human-hamster hybrid (A(L)) cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher (p < 0.01) in A(L) cells exposed to a cytotoxic concentration (1 mu mol/L) of MC-LR for 30 days than in untreated control cells, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide (NO) production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor N-G-methyl-L-arginine (L-NMMA), which suppressed MC-LRinduced mutations as well. The survival of mitochondrial DNA-depleted (rho(0)) A(L) cells was markedly decreased by MC-LR treatment compared to that in A(L) cells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis. (C) 2015 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences.
机译:微囊藻毒素-LR(MC-LR)是最丰富和毒性最大的微囊藻毒素同类物,已被国际癌症研究机构归类为潜在的人类致癌物(2B组)。但是,对MC-LR在慢性暴露过程中的遗传毒性作用的潜在机制仍知之甚少。在本研究中,人-仓鼠杂种(A(L))细胞暴露于MC-LR的时间长度不同,以研究氮自由基在MC-LR诱导的基因毒性中的作用。与未处理的对照细胞相比,暴露于MC-LR的细胞毒性浓度(1μmol / L)的A(L)细胞中,CD59基因座的诱变潜力高出2倍(p <0.01),这与微核的形成是一致的。 MC-LR导致处理过的细胞中一氧化氮(NO)产生剂量依赖性增加。此外,这可以通过同时用NO合酶抑制剂N-G-甲基-L-精氨酸(L-NMMA)来阻断,该抑制剂也抑制了MC-LR诱导的突变。与A(L)细胞相比,MC-LR处理可显着降低线粒体DNA贫化的(rho(0))A(L)细胞的存活率,而CD59突变级数则保持不变。这些结果提供了明确的证据,证明与哺乳动物细胞中慢性MC-LR暴露相关的遗传毒性是由NO介导的,并且可以被视为开发预防癌变的疗法的基础。 (C)2015年中国科学院生态环境研究中心。

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