Schedule dependence of buthionine sulfoximine in reversing resistance to cisplatin.
We have found that the potentiation of antiproliferative effects by buthionine sulfoximine (BSO) of cell growth inhibition induced by cisplatin are highly schedule dependent in resistant BE colon carcinoma cells. Maintenance of low GSH levels during the 12-h interval after cisplatin (cis-DDP) treatment is critical. A schedule of BSO exposure that results in low GSH levels for 12 h after cisplatin exposure is associated with a marked increase in DNA interstrand cross-link formation as analyzed by alkaline elution. These findings are consistent with a central role of GSH in interfering with the conversion of cis-DDP DNA monoadducts to DNA interstrand cross-links and may prove relevant to the design of clinical trials of BSO with cisplatin.
Robichaud
N J
NJ
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
Fram
R J
RJ
D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004351:Drug Resistance; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D003432:Cross-Linking Reagents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004247:DNA; D005978:Glutathione; D002945:Cisplatin