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J.Health Sci., 46(3), 182-186, 2000
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Methylmercury Toxicity at Cellular Levels - From Growth Inhibition to Apoptotic Cell Death -
Kyoko Miura
Department of Environmental Sciences, Faculty of Economics, Wako University, 2160 Kanai-cho, Machida-shi, Tokyo 195 -8585 and Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, 9 -1, Shirokane 5 chome, Minato-ku, Tokyo 108 -8641, Japan
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 beta-tubulin synthesis with little or no effect on total protein synthesis. This selective reduction in beta-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.
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