Abstract
Most cancer chemotherapeutic agents are designed to damage DNA directly or indirectly. One mechanism of cellular resistance to these agents is enhanced DNA repair. Human ovarian carcinoma cells resistant to cisplatin (A2780DDP) respond to cisplatin treatment with a 3–6-fold increase in gene expression for oncogenes, DNA repair enzymes and enzymes necessary for the synthesis of thymidine. Cyclosporin A has been shown to reverse drug resistance, but its mechanism of action is unclear. In this study, weekly exposures of A278ODDP cells to cyclosporin A resulted in the evolution of a revertant cell line A2780DDP/CSA that was sensitive to cisplatin again and suppressed the induction of genes necessary for the repair of drug-induced DNA damage.
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