REDUCED METHYLMERCURY ACCUMULATION IN A METHYLMERCURY-RESISTANT RAT PHEOCHROMOCYTOMA PC12 CELL-LINE

Rat pheochromocytoma PC12 cell sublines with increasing resistance to methylmercury (MeHg) were isolated by exposure to MeHg in two sequential steps. The strongest resistance (PC12/TM) among the clones obtained by the first cloning was characterized. PC12/TM cells exhibited about an 8- to 10-fold increase in resistance compared with parent PC12 cells on the bases of the concentration required for 50% inhibition of growth and colony-forming activity. PC12/TM cells accumulated smaller amounts of MeHg (one-half to one-fifth) than parent PC12 cells. This reduced MeHg accumulation in PC12/TM cells resulted from the slow uptake and rapid efflux. A close correlation between reduced MeHg accumulation and MeHg resistance was found among seven sublines of PC12 cells with different sensitivity to MeHg. The reduced retention of MeHg in PC12 sublines was also well correlated with the sensitivity to MeHg. Phenol-3,6-dibromophthalein disulfonate inhibited MeHg efflux from PC12/TM cells and increased its accumulation. These results suggest that efflux of MeHg from PC12/TM cells is associated with glutathione. © 1994 Academic Press, Inc.