Effect of glutathione on DNA repair in cisplatin-resistant human ovarian cancer cell lines.
We have studied the effect of glutathione reduction by buthionine sulfoximine (BSO), a specific inhibitor of gamma -glutamyl cysteine synthetase, on DNA repair after cisplatin damage in an ovarian cancer cell line with in vitro induced resistance to cisplatin. In addition, we have examined the effect of aphidicolin, a specific inhibitor of DNA polymerase alpha, in combination with BSO on cisplatin-associated DNA repair. BSO treatment was found to partially inhibit DNA repair, and the addition of aphidicolin caused nearly a 100% inhibition in DNA repair activity. Treatment of cells with glutathione ester after BSO resulted in complete recovery of DNA repair activity or partial recovery if aphidicolin was present. The significance of these results to the chemosensitizing effects of BSO medicated glutathione reduction is discussed.
Lai
G M
GM
Medicine Branch, National Cancer Institute, Bethesda, MD.
Ozols
R F
RF
Young
R C
RC
Hamilton
T C
TC
D016590:Aphidicolin; D019328:Buthionine Sulfoximine; D002499:Centrifugation, Density Gradient; D002945:Cisplatin / Q000494:pharmacology*; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004260:DNA Repair / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004224:Diterpenes; D008717:Methionine Sulfoximine; D016590:Aphidicolin; D019328:Buthionine Sulfoximine; D004257:DNA Polymerase II; D005978:Glutathione; D002945:Cisplatin