Subadditive interaction of radiation and taxol in vitro

Purpose/Objective: In vitro studies of taxol in combination with radiation indicate that taxol-mediated modification of radiation response is cell line dependent. It is also possible that the modifying action of taxol is critically dependent on the treatment protocol. Since taxol blocks cells in the G2 phase of the cell cycle it was hypothesized that if the G2 block was maintained for several hours during the post-irradiation period by holding in taxol, thus allowing more time for repair of radiation damage, that radiation survival would be enhanced. Materials and Methods: The human laryngeal squamous cell carcinoma cell line SCC20 was used for this study. Cells were irradiated as subconfluent cultures using Cs-137 gamma rays at a dose-rate of 1.8 cGy/min. Cultures were pretreated with taxol (7.5nM for 12h, S.F. = 0.4) and then irradiated with graded doses followed either by immediate plating, or holding for 6h either in the absence or presence of 7.5nM taxol prior to plating for colony forming ability. Experiments in which cells were irradiated and then exposed to 7.5nM taxol for both 12 and 18h were also performed. Parallel flow cytometric analyses of the cell cycle distribution of the various treated populations were carried out. Results: The results indicate that pretreatment with taxol induced a G2 block which was maintained during 6h post-irradiation holding either in the absence or presence of taxol. No modification of radiosensitivity was seen for cells treated with taxol, irradiated and plated immediately with the resulting survival being compatible with an additive effect. This is consistent with several observations in the literature which used a similar protocol with other cell lines. However, for taxol-pretreated cells held for 6h post-irradiation, either in the absence or the presence of taxol, the resulting survival reproducibly demonstrated a marked less than additive effect. This was particularly prominent for cells held in the presence of taxol. Subsequent experiments in which taxol was added to cells immediately after irradiation again demonstrated a less than additive effect of the two modalities. Conclusion: The results of this study are consistent with a dual mechanism of taxol-induced radiation resistance, possibly as a consequence of post-irradiation holding in G2, and the radiation-induction of resistance to taxol-induced cellular lethality through an as yet undefined mechanism. The findings of this study have potentially great significance to the combined use of taxol and radiation in clinical cancer therapy where, contrary to the popular notion of taxol as a potential radiosensitizer, it may be that the combined treatment is less than additive