Paclitaxel exposure time determines the nature of the interaction with radiation in HeLa cells: the role of apoptosis

The purpose of the present study was to investigate further the mechanisms underlying subadditive and superadditive interactions of radiation and pacl itaxel treatments in vitro. The protocol studied was a fixed radiation trea tment (7 Gy) followed either immediately or after a 10 h delay by paclitaxe l treatment. Paclitaxel treatment was exposure to either a fixed dose of pa clitaxel (10 nM) for varying time intervals up to 25 h, or varying doses of paclitaxel up to 20 nM for a fixed exposure time of 24 h. The cells used w ere HeLa. Cell survival was assessed by colony forming ability and apoptosi s was measured by flow cytometry. The results show that when the paclitaxel exposure time was 24 h superadditive interactions were observed at all pac litaxel doses. A reasonable correlation between surviving fraction as measu red by colony forming ability and apoptosis in the attached cells at the en d of paclitaxel treatment was observed. The nature of the interaction of ra diation and subsequent paclitaxel treatment is critically dependent on the duration of the paclitaxel treatment. (C) 2000 Elsevier Science Ltd. All ri ghts reserved.