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. 相似文献
With a growing awareness of environmental protection, the dust pollution caused by automobile foundry work has become a serious and urgent problem. This study aimed to explore contamination levels and health effects of automobile foundry dust. A total of 276 dust samples from six types of work in an automobile foundry factory were collected and analysed using the filter membrane method. Probabilistic risk assessment model was developed for evaluating the health risk of foundry dust on workers. The health risk and its influencing factors among workers were then assessed by applying the Monte Carlo method to identify the most significant parameters. Health damage assessment was conducted to translate health risk into disability-adjusted life year (DALY). The results revealed that the mean concentration of dust on six types of work ranged from 1.67 to 5.40 mg/m3. The highest health risks to be come from melting, cast shakeout and finishing, followed by pouring, sand preparation, moulding and core-making. The probability of the risk exceeding 10−6 was approximately 85%, 90%, 90%, 75%, 70% and 45%, respectively. The sensitivity analysis indicated that average time, exposure duration, inhalation rate and dust concentration (C) made great contribution to dust health risk. Workers exposed to cast shakeout and finishing had the largest DALY of 48.64a. These results can further help managers to fully understand the dust risks on various types of work in the automobile foundry factories and provide scientific basis for the management and decision-making related to health damage assessment.