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Interaction of Ionizing Radiation with Paclitaxel (Taxol) and Docetaxel (Taxotere) in HeLa and SQ20B Cells¹

Unité 350 INSERM, Institut Curie-Biologie, Bâtiments 110-112, Centre Universitaire, 91405 Orsay Cedex [N. G., V. F.], and Service de Radiothérapie-Oncologie, Hôpital Saint-Louis, 1 Avenue Claude-Vellefaux, 75010 Paris [C. H.], France

Altered -ray response by brief (1 h), concomitant exposure to paclitaxel (Taxol) or docetaxel (Taxotere) was investigated in growing HeLa and SQ20B human tumor cells in vitro. For both cell lines, both taxoids were able to reduce or enhance radiation cell killing, depending on the drug concentration. Large reduction of radiosensitivity (up to 3.3-fold reduction relative to radiation alone) was observed in HeLa cells over a wide range of drug concentrations, extending to 1.5- (paclitaxel) or 3.3-fold (docetaxel) the IC₅₀s determined for drug alone. This antagonistic effect was also observed with SQ20B cells. It disappeared for drug concentrations exceeding 0.9 (SQ20B), 1.6 (HeLa; paclitaxel), and 3.4 (HeLa; docetaxel) IC₅₀ equivalents, above which a drug dose-dependent, supraadditive radiation-drug interaction was observed.

Reduction of radiation susceptibility in the low-drug dose range also held for mid-G₁ synchronized HeLa cells, i.e., in the cell cycle compartment characterized as the most resistant one to docetaxel (C. Hennequin et al., Br. J. Cancer, 71: 1194–1198, 1995). In the case of SQ20B cells, the cytotoxicity of either drug or radiation alone was primarily dependent on the state of growth, with quiescent (G₀) cells showing increased radiosensitivity and reduced drug toxicity compared to the growing fraction.

The effect of taxoids (1-h contact) was finally investigated in sequential treatment as a function of the time elapsed between radiation and exposure to drugs. In HeLa cells, the postirradiation time-dependence of the response to combined treatment was biphasic. The radioprotecting potential of either taxoid disappeared in 1.5 h following radiation. At longer postirradiation delays, radiation-induced redistribution in the cell cycle appeared to be the major determinant of HeLa cell survival, in relation to the differential cell cycle phase specificity of each drug. Pronounced paclitaxel recovery versus increased sensitivity to docetaxel occurred over 8 h after irradiation. SQ20B cells showed monophasic radiation recovery with both drugs over the same time range.

¹ This work was supported by the Institut National de la Santé et de la Recherche Médicale (to V. F.) and by Rhône-Poulenc Rorer S. A.

² To whom requests for reprints should be addressed. Phone: (33) 1-6986-3188; Fax: (33) 1-6986-3187; E-mail: Favaudon@iris.curie.u-psud.fr.

Received 11/ 2/95. Accepted 2/14/96.

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