Effect of docetaxel (Taxotere) on expression of radiation-induced lethal mutations in human cell lines.
OBJECTIVE
To investigate if docetaxel, ionizing radiation or a combination of both induces delayed cell death in selected human normal or tumour cell lines.


METHODS
The initial and residual surviving fractions were determined for two malignant human colon cell lines of widely different radiosensitivity (SW 48 and HT29) and for an immortal but non-malignant human keratinocyte line (HaCaT).


RESULTS
Lethal mutations were observed only after the treatment of SW48 and HaCaT cells with radiation alone. No lethal mutations were found in the HT29 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.


CONCLUSIONS
In all cases a combination of radiation and docetaxel prevented induction of lethal mutations despite the fact that radiation alone induced 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 inhibiting the lethal mutation pathway. There appears to be a link between the tendency of the cell line to undergo apoptosis and lethal mutation expression.
Radiation Science Centre, Dublin Institute of Technology, Ireland.
M
M
Creane
C B
CB
Seymour
C
C
Mothersill
D000077143:Docetaxel; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009154:Mutation / Q000187:drug effects*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D043823:Taxoids; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D051028:bcl-2-Associated X Protein; D000077143:Docetaxel; D017239:Paclitaxel