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Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human–hamster hybrid cells
摘    要: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 ALcells 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-LRinduced mutations as well. The survival of mitochondrial DNA-depleted(ρ0) ALcells was markedly decreased by MC-LR treatment compared to that in ALcells, 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.


Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human-hamster hybrid cells
Authors:Xiaofei Wang  Pei Huang  Yun Liu  Hua Du  Xinan Wang  Meimei Wang  Yichen Wang
Institution:1. Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031,Anhui, China;Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui, China
2. Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031,Anhui, China
Abstract:
Keywords:Microcystin-LR (MC-LR)  Chronic exposure  Genotoxicity  Nitric oxide
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