Lai G M, Ozols R F, Young R C, Hamilton T C
Medicine Branch, National Cancer Institute, Bethesda, MD.
J Natl Cancer Inst. 1989 Apr 5;81(7):535-9. doi: 10.1093/jnci/81.7.535.
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.
我们研究了丁硫氨酸亚砜胺（BSO）（γ-谷氨酰半胱氨酸合成酶的特异性抑制剂）降低谷胱甘肽对体外诱导的顺铂耐药卵巢癌细胞系顺铂损伤后DNA修复的影响。此外，我们还研究了DNA聚合酶α的特异性抑制剂阿非科林与BSO联合使用对顺铂相关DNA修复的影响。发现BSO处理可部分抑制DNA修复，而添加阿非科林会导致DNA修复活性几乎100%被抑制。BSO处理后用谷胱甘肽酯处理细胞，若不存在阿非科林，DNA修复活性可完全恢复；若存在阿非科林，则可部分恢复。本文讨论了这些结果对BSO介导的谷胱甘肽降低的化学增敏作用的意义。
