PROLIFERATION AND CLONAL SURVIVAL OF HUMAN LUNG-CANCER CELLS TREATED WITH FRACTIONATED-IRRADIATION IN COMBINATION WITH PACLITAXEL

Purpose: This study was performed to determine the effects of a contin uous exposure to paclitaxel (taxol) in combination with fractionated i rradiation on cell proliferation and survival. Methods and Materials: Human lung carcinoma cells (SW1573) were given a daily treatment with 3 Gy of x-rays during 5 days in the continuous presence of 5 nM taxol, The surviving fraction and the total number of cells were determined every 24 h before and immediately after irradiation. Results: Irradiat ion with 5 x 3 Gy and 5 nM taxol cause approximately the same inhibiti on of cell proliferation, In combination these treatments have an addi tional effect and the cell population increases no further after the f irst 24 h, Whereas the cells become more resistant to taxol after the first 24 h with a minimum survival of 42%, taxol progressively reduces the population of surviving cells in combination with x-rays when the number of fractions increases, up to 25-fold relative to irradiation alone, The enhancement effect of 5 nM taxol is likely to be attributed to an inhibition of the repopulation during fractionated irradiation and not to an increased radiosensitivity, Only after treatment with 10 or 100 nM taxol for 24 h, which is attended with a high cytotoxicity, is moderate radiosensitization observed. Conclusion: Taxol, continuou sly present at a low concentration with little cytotoxicity, causes a progressive reduction of the surviving cell population in combination with fractionated irradiation, mainly by an inhibition of the repopula tion of surviving cells between the dose fractions.