Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human-hamster hybrid cells

Journal of Environmental Sciences (China)
Xiaofei WangAn Xu

Abstract

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 (AL) 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 AL cells exposed to a cytotoxic concentration (1 μmol/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 NG-methyl-L-arginine (L-NMMA), which suppressed MC-LR-induced mutations as well. The survival of mitochondrial DNA-depleted (ρ0) AL cells was markedly decreased by MC-LR treatment compared to that in AL cells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with c...Continue Reading

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Citations

Sep 12, 2015·Journal of Environmental Sciences (China)·Bingsheng Zhou
May 15, 2015·Journal of Environmental Sciences (China)·Qingqing Liu, X Chris Le
Jul 4, 2020·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Muhammad KhisroonAbid Ullah
Mar 18, 2020·Ecotoxicology and Environmental Safety·Xiaofei WangShaopeng Chen

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