Methylmercury Toxicity at Cellular Levels : From Growth Inhibition to Apoptotic Cell Death

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This review describes our studies on the toxic effects of methylmercury (MeHg) at cellular levels using neuroblastoma, PC12,glioma and HeLa cell lines. MeHg specifically disrupted microtubules and inhibited cell growth by halting the cell cycle at the M phase. Effects on DNA, RNA and protein syntheses were not associated with growth inhibition by MeHg. Microtubule disruption by MeHg led to specific inhibition of β-tubulin synthesis with little or no effect on total protein synthesis. This selective reduction in β-tubulin synthesis was caused by post-transcriptional regulation through increased an tubulin pool resulting from depolymerization of microtubules by MeHg. The cells exposed to MeHg proceeded to apoptotic cell death long after growth inhibition. Since the occurrence of apoptosis was preceded by the G2/M phase arrest after MeHg treatment, it is likely that this arrest is an important event in apoptosis induction by MeHg. This apoptosis was induced via a p53-independent pathway in neuronal and nonneuronal cell lines. The study using the MeHg resistant cell line established by us demonstrated that the ability to accumulate MeHg and a low level of intracellular glutathione(GSH) made cells to vulnerable to MeHg.The neuronal cell lines showed a tendency to have a lower GSH level and, consequently, a higher susceptibility to MeHg than nonneuronal cell lines.
公益社団法人日本薬学会の論文
2000-06-01