THERMOSENSITIVITY AND THERMOTOLERANCE IN THE ADRIAMYCIN-RESISTANT STRAIN OF EHRLICH ASCITES TUMOR-CELLS

The acquisition of resistance to anticancer drugs is an important prob lem in cancer chemotherapy. Ehrlich ascites tumor cells (wild type EAT cells) were grown in a medium containing 1 mu g/ml adriamycin (ADR) ( ADR-resistant strain) and the cells that proliferated were established in our laboratory. Intracellular ADR accumulation and the killing eff ect of ADR in the ADR-resistant strain were markedly reduced compared with those of the wild type EAT cells. In this study, we initially obs erved thermosensitivity in both strains and found no difference in the thermosensitivity. These findings demonstrated that hyperthermic trea tment was effective in the ADR-resistant strain as well as in the wild type EAT cells. On the other hand, thermotolerance is an important pr oblem in the hyperthermic treatment of cancer. We next observed the th ermotolerance of both strains and found that the thermotolerance in th e ADR-resistant strain was greater than that in the wild type EAT cell s, but the thermotolerance was almost restored within 24 hours. Furthe rmore, we investigated the influence of thermotolerance on the intrace llular accumulation and killing effects of ADR in the wild type EAT ce lls. There was no difference in the intracellular ADR accumulation and the killing effect of ADR between non-thermoresistant cells and therm oresistant cells. These results suggested that hyperthermia was effect ive in the ADR-resistant cells either alone or combination with ADR.