Mechanisms of cisplatin (cis-diamminodichloroplatinum II)-induced cytotoxicity and genotoxicity in yeast |
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Authors: | M A Hannan S G Zimmer J Hazle |
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Affiliation: | 1. McDowell Cancer Network, University of Kentucky, 915 S. Limestone, Lexington, KY 40536, USA;2. Department of Pathology, University of Kentucky Medical Center, Lexington, KY 40536 U.S.A. |
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Abstract: | The antitumor drug, cisplatin (cis- diamminodichloroplatinum II), dissolved in both water and phosphate-buffered saline, was studied for its genotoxic and cytotoxic effects in the yeast, Saccharomyces cerevisiae. The results showed that the drug was both recombinagenic and mutagenic in the wild-type diploid strain D7. It was observed that both cytotoxicity and genotoxicity were greatly reduced when cisplatin was dissolved in phosphate-buffered saline compared to the aqueous solution. Cell survival analyses showed that the diploid strain (D7 rad 3), deficient in excision of UV-induced pyrimidine dimers or similar adducts, was hypersensitive to cisplatin. Another diploid strain (rad 52/rad 52), blocked in the repair of DNA double-strand breaks and recombination was also hypersensitive to the drug. Mitotic gene conversion was not observed in the rad 52/rad 52 diploid after the drug treatments, while it was reduced in the excision -deficient strain. Reverse mutations occurred in the excision-deficient strain (D7 rad 3), even at low doses of cisplatin. These results are discussed in relation to the possible mechanisms of cisplatin-induced cell death and genotoxicity. |
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Keywords: | All correspondence and reprint requests to: Dr. Mohammed A. Hannan Department of Cancer and Radiation Biology Cancer Therapy Institute King Faisal Specialist Hospital and Research Centre P.O. BOX 3354 Riyadh 11211 Saudi Arabia. |
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