Modulation of radiosensitivity in Chinese hamster lung fibroblasts by cisplatin

Abstract

The effects of cisplatin exposure time, concentration, and irradiation sequence on the sensitivity of Chinese hamster lung fibroblasts (V79) to γ-ray exposure were examined. Based on clonogenic cell survival, the cisplatin concentrations corresponding to 50% cell survival (EC50) for exposure times of 1 h to 7 days followed a 2-phase exponential decay and ranged from 28.26 ± 3.32 to 1.53 ± 0.24 μmol/L, respectively. When cells were treated at EC50 for exposures of less than 4 h and irradiated immediately, cisplatin inhibited the effect of radiation. Exposures of 4–6 h did not affect radiosensitivity. For exposures of 8–12 h, radiosensitization was observed, which disappeared at 14 h and reappeared for much longer cisplatin treatments. At the lowest achievable EC50 (1.53 μmol/L), radiosensitization was observed if irradiation was delayed for 1–8 h. This enhancement in radiosensitivity disappeared for irradiation delays of 10–12 h, but reappeared when irradiation was delayed for 14–18 h. These data demonstrate that the mode of interaction between cisplatin and γ-irradiation depends on the concentration and exposure time of cisplatin, as well as on the timing of irradiation after cisplatin administration. Consideration of changes in cell cycle kinetics may contribute to the improvement of treatment outcomes in adjuvant chemoradiotherapy involving cisplatin.