Radiation sensitization of chinese hamster V79 cells by paclitaxel

摘要

AbstractBecause paclitaxel has been reported to disrupt microtubules and block cells in G2/M of the cell cycle, the radiation response of Chinese hamster V79 cells exposed to various paclitaxel concentrations and durations of exposure was evaluated. Parallel to clonogenic cell survival studies, paclitaxel‐mediated perturbations on the cell cycle were also assessed by flow cytometry. While short‐term incubation (0–6 hr) with 0.1, 1, or 10 μM paclitaxel caused a gradual accumulation of cells into G2/M, no radiosensitization was observed. Incubation with 0.05—1 μM paclitaxel for 12 hr followed by X‐ray treatment resulted in radiosensitization (enhancement ratio at the 10 survival level = 1.7). Paclitaxel concentrations above 1 μM had similar effects on the cell cycle at lower concentrations, yet radiosensitization decreased such that at 10 μM no radiosensitization was observed. Likewise, no radiosensitization was observed for cells incubated for 24 hr with 0.1, 1 or 10 μM paclitaxel and irradiated. Cell cycle analysis indicated that cells receiving less than 0.25 μM paclitaxel for 12 hr were only transiently blocked in mitosis and then went on to complete mitosis; cells receiving greater than 0.25 μM paclitaxel for 12 hr or more became polyploid, i.e., cells moved into a semisynchronous tetraploid G1 state. (Cells irradiated at 24 hr had progressed to a tetraploid G2 state.) Taken as a whole, these results indicate that paclitaxel‐mediated radiosensitization and cell cycle perturbation are both time and concentration dependent. © 1993 Wiley‐Liss, IncThis article is a US government work and, as such, is in the public domain in the Unit