Effect of Glutathione on DNA Repair in Cisplatin-Resistant Human Ovarian Cancer Cell Lines

We have studied the effect of glutathione reduction by buthionine sulf-oximine (BSO), a specific inhibitor ofλ -glutamyl cysteine synthetase, on DNA repair after cisplatin damage in an ovarian cancer cell line with invitro induced resistance to cisplatin. In addition, we have examined the effect of aphidicolin, a specific inhibitor of DNA polymerase a, in combination with BSO on cisplatin-associated DNA repair. BSO treatment was found topartially inhibit DNA repair, and the addition of aphidicolin caused nearly a100% inhibition in DNA repair activity. Treatment of cells with glutathioneester after BSO resulted in complete recovery of DNA repair activity or par-tial recovery if aphidicolin was present. The significance of these results to the chemosensitizing effects of BSO medi-ated glutathione reduction is discussed. [J Natl Cancer Inst 81:535-539, 1989]