Effect of docetaxel (taxotere) on expression of radiation-induced lethal mutations in human cell lines

Purpose: To investigate if docetaxel, ionizing radiation or a combination o f both induces delayed cell death in selected human normal or tumour cell l ines. Materials and methods: The initial and residual surviving fractions were de termined for two malignant human colon cell lines of widely different radio sensitivity (SW 48 and HT29) and for an immortal but non-malignant human ke ratinocyte line (HaCaT). Results: Lethal mutations were observed only after the treatment of SW48 an d HaCaT cells with radiation alone. No lethal mutations were found in the H T29 cell line. No lethal mutations were observed for any cell line treated with Docetaxel and the plating efficiency of progeny was actually increased above the control level. Conclusion: In all cases a combination of radiation and docetaxel prevented induction of lethal mutations despite the fact that radiation alone induce d lethal mutations in the SW48 and HaCaT cell lines. This suggests that the effects of pre-treating with Docetaxel are in some way blocking or inhibit ing the lethal mutation pathway. There appears to be a link between the ten dency of the cell line to undergo apoptosis and lethal mutation expression.