Nuclear DNA Damage and Repair in Normal Ovarian Cells Caused by Epothilone B

Abstract

This study was designed to assess, whether a new chemotherapeutic microtubule inhibitor, Epothilone B(EpoB, Patupilone), can induce DNA damage in normal ovarian cells (MM14.Ov), and to evaluate if such damagecould be repaired. The changes were compared with the effect of paclitaxel (PTX) commonly employed in theclinic. The alkaline comet assay technique and TUNEL assay were used. The kinetics of DNA damage formationand the level of apoptotic cells were determined after treatment with IC50 concentrations of EpoB and PTX. Itwas observed that PTX generated significantly higher apoptotic and genotoxic changes than EpoB. The peakwas observed after 48 h of treatment when the DNA damage had a maximal level. The DNA damage induced byboth tested drugs was almost completely repaired. As EpoB in normal cells causes less damage to DNA it mightbe a promising anticancer drug with potential for the treatment of ovarian tumors.

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