Glutathione content is correlated with the sensitivity of lines of PC12 cells to cisplatin without a corresponding change in the accumulation of platinum

A study of the involvement of glutathione (GSH) in cellular resistance to c isplatin was performed using methylmercury-resistant sublines (PC12/TM seri es) of the PC12 line of rat pheochromocytoma cells. The seven clonal sublin es of PC12 cells (PC12/TM, PC12/TM2, PC12/TM5, PC12/TM11, PC12/TM15, PC12/T M23, PC12/TM26) used in the study had intracellular levels of GSH that rang ed from 8.7-39.9 nmol/mg protein. The intracellular level of GSH was signif icantly correlated (p < 0.01, r = 0.87) with the sensitivity to cisplatin o f PC12 cells and the seven sublines. Among the seven sublines, PC12/TM cell s contained the highest concentration of GSH and were the most resistant to cisplatin. Treatment of PC12/TM cells with L-buthionine-SR-sulfoximine, wh ich reduced the level of GSH to that in the parental PC12 cells, significan tly reduced the resistance of the cells to cisplatin. The amount of platinu m accumulated by resistant PC12/TM cells after treatment with cisplatin was higher than that by sensitive PC12 cells. These results suggest that the i ntracellular level of GSH might be directly involved in the resistance to c isplatin of these cell lines. However, a high intracellular concentration o f GSH does not appear to contribute to a decrease in the accumulation of ci splatin in these cells.