Heat sensitization to cisplatin in two cell lines with different drug sensitivities

Heat sensitization to cisplatin was studied in drug-sensitive Chinese hamster fibroblast (CH) and inherently drug-resistant hamster kidney (HaK) cells. Under normothermic conditions the slopes of the survival curves differed by a factor of 3.6, while the cellular uptake was higher in CH cells by a factor of 3. When heat and drug treatment were given simultaneously, both effects were increased in CH and HaK cells: thermal enhancement factors at 43 degrees C were 5.5 (CH) and 2.9 (HaK) for cytotoxic drug action and 3.9 and 2.2 for the increase in cellular drug content. Increase in cell sensitization was also obtained if the cells were heat pretreated (42.5-44 degrees C for various times) followed by drug exposure at 37 degrees C. It is concluded that thermal enhancement depends on the efficiency of cisplatin cytotoxicity, which in turn correlates with cellular drug uptake in both the sensitive and resistant cell line.