Cytoprotective effects of amifostine and cysteamine on cultured normal and tumor cells treated with paclitaxel in terms of mitotic index and H-3-thymidine labeling index

Abstract

Purpose: In this study, the cytotoxic effects of paclitaxel (PAC) in normal and tumor cells were established, and the cytoprotective effects of amifostine (AMI) and cysteamine (CYS) against this cytotoxicity were examined. Methods: Tumor cell lines used in this study were L-strain cells of mouse subcutaneous origin and human cervix carcinoma-derived HeLa cells. Mouse embryonic fibroblasts (MEFs) were used as the normal cell line. Results of the experiments were evaluated in terms of the mitotic index and the H-3-thymidine labeling index. PAC concentrations of 6 and 12 mu g/ml were applied to the cells for 1-10 days either alone or in combination with 1 mu g/ml of AMI and CYS. Results: In terms of the above parameters, statistically significant effects were not seen in cultures of any of the cell lines treated with 1 mu g/ml of AMI or CYS alone. In contrast, both concentrations of PAC caused increasing cytotoxic effects with increasing treatment time (P < 0.001). The cytotoxic effect of PAC appeared as mitotic phase accumulation (G(2)/M blockage) and a subsequent decline in the synthesis phase. HeLa cells were very sensitive to PAC treatment, whereas MEF cells were quite resistant compared with tumor cells. In cells treated with combined drugs to investigate the cytoprotective effects of AMI and CYS on normal and tumor cell lines, PAC continued to show cytotoxic effects in tumor cells, but this effect was reduced in the normal cells. Conclusions: AMI and CYS did not protect tumor cells against the cytotoxic effects of PAC, but protection was observed in normal cells. Furthermore, the protection provided by AMI was stronger than that provided by CYS.