Effect of Chemotherapy on the Mutation Frequency of Ovarian Cancer Cells at the HPRT Locus

Abstract

Objective: Resistance to chemotherapy in ovarian cancers is a difficult problem. Our objective was to demonstrate the effect of chemotherapeutic agents, used in the treatment of ovarian cancer, on the mutation frequency of ovarian cancer cells at the HPRT locus. Materials and Methods: Single cell clones were isolated from a recently established ovarian cancer cell line. The cells were then exposed to sublethal doses of cisplatin, paclitaxel or topotecan. After recovering from the cytotoxic effect of these agents, mutation frequencies of the treated and control cells were determined in 6-thioguanine. Results: Recovery from chemotherapeutic agents was variable among clones. Cisplatin had 5/8 clones showing an enhancement in the induced mutation frequency. Paclitaxel had only 1/7 clones showing a positive increase in the induced mutation frequency, the parent line. Finally topotecan had 3/8 colonies showing an accelerated induced mutation frequency. A total of 9/23 clones with an accelerated induced mutation frequency were identified following various chemotherapeutic agents. Conclusion: We demonstrated that, in a limited number of colonies from an ovarian cancer, there was an ability to increase the mutation frequency at the HPRT locus after exposure to common chemotheraputics used in the treatment of this disease. This induction of more mutations by chemotherapy may help explain the developing chemoresistance of this disease during or following treatment.