International journal of cancer. Journal international du cancer
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Glutathione (GSH) has often been implicated in the mechanism of resistance to platinum anti-cancer drugs. It has been suggested that GSH may reduce the cytotoxicity of these drugs by forming inactive conjugates and by enhancing the repair of DNA-platinum crosslinks. In the present study we have examined the effect of D,L-buthionine-S,R-sulfoximine (BSO) pretreatment on the accumulation of platinum in a sensitive (CHI) and 2 relatively resistant (SKOV-3, HX/62) human ovarian-carcinoma cell lines following exposure to PtII- (cisplatin, carboplatin) and PtIV-drugs (tetraplatin). ⋯ However, concomitant increases in intracellular levels of reactive species were observed only after tetraplatin exposure. Our data suggest that the greater potentiation of PtIV- compared with PtII-drug cytotoxicity in the relatively resistant cell lines following 24 hr BSO pre-treatment may be caused by a differential effect of BSO on the metabolism and cellular distribution of these drugs. A BSO-induced reduction in PtII- but not PtIV-drug accumulation in these cells may also partially contribute to the differential potentiation of cytotoxicity of these drugs.