| Research Abstract |
Stable sublines of rat pheochromocytoma PC12 cells, which are resistant to methylmercury (MeHg), have been established. The most resistant subline (PC12/TM) among the clones obtained by the first cloning were further characterized. The resistant cells accumulated smaller amounts of MeHg than the parent PC12 cells. This decrease in MeHg accumulation in PC12/TM cells resulted from the slow uptake and rapid efflux of the MeHg. An inverse correlation between MeHg accumulation and MeHg resistance was found among 7 sublines of PC12 cells with varying sensitivity to MeHg. Treatment of PC12/TM cells with DBSP, an agent to block efflux of MeHg from the cells, increased the sensitivity of PC12/TM cells to MeHg. Intracellular GSH level in PC12/TM cells was 4-times higher than that of PC12 cells. Pretreatment of PC12/TM cells with BSO, which reduced the GSH level to that of parent PC12 cells, increased the sensitivity of PC12/TM cells to MeHg. Since the accumulation of MeHg in PC12/TM cells was not increased by the treatment with BSO, the intracellular GSH may prevent cell damage by interrupting MeHg binding to the target molecules in the cells.
From these results it was concluded that the extent of MeHg accumulation and intracellular GSH level might play important roles in determining the sensitivity of PC12 and its sublines to MeHg.
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