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

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 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.

DOI: 10.1016/j.jes.2014.07.036

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@article{Wang2015RoleON, title={Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human-hamster hybrid cells.}, author={Xiaofei Wang and Pei Huang and Yun Liu and Hua X. Du and Xin'an Wang and Meimei Wang and Yichen Wang and Tom K. Hei and Lijun Wu and An Xu}, journal={Journal of environmental sciences}, year={2015}, volume={29}, pages={210-8} }