162 Differential effect of the chemotherapeutic agent taxol on the radiosensitivity of normal human fibroblasts and human tumour cells in vitro

Abstract

In order to analyze the radiosensitizing potency of taxol, <i>in vitro</i> culture studies were performed using normal human skin fibroblasts and human tumour cell lines derived from squamous cell carcinomas. Dose response curves based on clonogenic assays revealed that a concentration of 5 nM resulted in a significant inhibition of cell growth for both normal and tumour cell lines by 30–80%. When the cells were irradiated with 2 Gy or with increasing doses of ionizing radiation after preincubation of 24, 48 or 72 h with taxol a significant difference: in the radiosensitivity of normal skin fibroblasts and human tumour cells was apparent demonstrating a more pronounced radiosensitizing effect on tumour cells, as compared to normal cells. Although taxol has been described to induce a G₂/M-block, ongoing cell cycle analyses revealed that the increment in radiosensitivity of human tumour cells did not necessarily correlate to a possible induction of the G₂/M-block in the cells treated. Thus, it can be concluded that taxol may exert specific radiosensitizing effects on human tumour cells, but not on normal diploid cells. Experiments are in progress to elucidate the specific cell biological and molecular mechanisms of the radiosensitizing effect of taxol on squamous cell carcinoma cells. On the basis of these data strategies for the use of taxol in radiooncoloy can be developed.