Modification of multidrug resistance of tumor cells by ionizing radiation

Purpose The effect of ionizing radiation on multidrug resistance (MDR) of human larynx cancer HEp-2 cells has been investigated. We studied the dependence of the radiation effect on radiation dose, time after irradiation and cell density. Methods MDR was determined from an increase in cell sensitivity to daunorubicin, taxol and vincristine by the inhibitors of multidrug resistance cyclosporin A and avermectin B-1, and from the suppression by cyclosporin A of the transport of rhodamine 123 out of the cells. The cells were irradiated with X-ray beams (dose rate 1.12 Gy min(-1)) at room temperature. Results It was shown that, at 8 and 16 h after irradiation with doses up to 4 Gy, the multidrug resistance of cells increases, and at 24 h it decreases to the control level. The effect was maximal by 16 h after irradiation with a dose of 1 Gy. Both, the contribution of active transport to the rate of rhodamine 123 efflux from cells and their resistance to vincristine, increased. The effect of irradiation on multidrug resistance of HEp-2 cells depended on the density of cells on the substrate, being maximal at a density of 80,000-100,000 cm(-2). Conclusion The irradiation-induced changes in the MDR of tumor cells should be taken into account when combining radiotherapy with chemotherapy. It was assumed that the dependence of multidrug resistance of HEp-2 cells on radiation dose and cell density is determined by changes in the amount of reactive oxygen species in the cells.