Radiosensitization in sarcoma cell lines with a p53 missense mutation correlates with prevention of irradiation G2/M arrest but not with induction ofapoptosis

We analysed the effects of caffeine and taxol on the radiobiological behavi our of two human sarcoma cell lines (RD, SK-LMS-1) each with a p53 missense Mutation. Treatment with 2 mM caffeine resulted in an inhibition of the ir radiation induced G2/M arrest in both cell lines. This effect was coupled w ith a radiosensitization in cell line SK-LMS-1 after an irradiation with 6 Gy (enhancement factor of 5.0). However, the effect of radiosensitization w as not correlated with an induction of apoptosis. Incubation with 20 nM tax ol increased the irradiation induced apoptosis almost 3-fold in cell line S K-LMS-1, but not in cell line RD. However, taxol had no effect on the irrad iation induced G2/M at-rest or radiosensitivity in either cell line. The re sults Support the hypothesis that the prevention of irradiation induced G2/ M arrest but not the induction of apoptosis plays a critical role in determ ining radiosensitivity in sarcoma cell lines with p53 mutations.