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Effect of Glutathione on DNA Repair in Cisplatin-Resistant Human Ovarian Cancer Cell Lines
Abstract
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.
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Citations
Cited by
Cellular processing of platinum anticancer drugs
Wang, D., & Lippard, S. J. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1691 · Cited by 3,801
Ovarian cancer: strategies for overcoming resistance to chemotherapy
Agarwal, R., & Kaye, S. B. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1123 · Cited by 1,154
Meister, A. (1991) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(91)90076-x · Cited by 907
Mechanisms of resistance to cisplatin
Kartalou, M., & Essigmann, J. M. (2001) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/s0027-5107(01)00141-5 · Cited by 869
Cellular and molecular determinants of cisplatin resistance
Perez, R. P. (1998) · European Journal of Cancer · doi:10.1016/s0959-8049(98)00227-5 · Cited by 384
Metadata
- Authors
- Lai, G.-M., Ozols, R. F., Young, R. C., & Hamilton, T. C.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1989-04-05
- Volume
- 81
- Issue
- 7
- Pages
- 535-539
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2042320307
- Cited by
- 167
- References
- 0
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Effect of Glutathione on DNA Repair in Cisplatin-Resistant Human Ovarian Cancer Cell Lines. https://app.cochat.ai/papers/10.1093/jnci/81.7.535
- The paper
- Lai, G.-M., Ozols, R. F., Young, R. C., & Hamilton, T. C. (1989). Effect of Glutathione on DNA Repair in Cisplatin-Resistant Human Ovarian Cancer Cell Lines. JNCI Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/81.7.535
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
