Differential Potentiation of Alkylating and Platinating Agent Cytotoxicity in Human Ovarian Carcinoma Cells by Glutathione Depletion

摘要: We have determined the effect of glutathione (GSH) depletion on cytotoxicity three nitrogen mustards, six platinum complexes, and mitomycin C in a human ovarian carcinoma cell line. GSH levels COLO 316 cells were depleted by exposure monolayers to 0.5 mm d,l-buthionine- S,R -sulfoximine. significantly potentiated l-phenylalanine mustard, chlorambucil, mechlorethamine as clonogenic assay plastic plates. The dose modification factors 2.6, 1.9, respectively. same level had minimal cis -diamminedichloroplatinum(II) (cis-DDP), carboplatin, dichloro(ethylenediamine)platinum(II), 1,2-diaminocyclohexylplatinum(II) malonate, iproplatin. for these drugs 1.4 or less. trans -Diamminedichloroplatinum(II) was, however, markedly with factor 2.7. Mitomycin was minimally depletion. also generated cis-DDP-resistant from 2008 vitro selection cis-DDP. These identical parental cells. sensitized only degree did not reverse resistant phenotype. Our results indicate that intracellular are an important determinant -platinum(II) -platinum(IV) complexes In addition, altered metabolism does appear be component phenotype