Synergistic enhancement of bleomycin cytotoxicity toward tumor cells in culture by a combination of ethanol and moderate hyperthermia.

Bleomycin cytotoxicity toward mouse mammary carcinoma FM3A cells and human carcinoma HeLa S3 cells in culture was greatly potentiated by exposing the cells to a combination of a low concentration of ethanol and moderate hyperthermia. For example, the exposure of FM3A cells to a combination of 4.3% ethanol and 39 degrees, 2.4% ethanol and 41 degrees or 1.5% ethanol and 42 degrees induced a marked sensitization which was almost equivalent to that induced by exposure to 6% ethanol at 37 degrees and was greater than that induced by exposure to 43 degrees hyperthermia alone. However, when the cells were exposed to 3% ethanol at 37 degrees and then treated with bleomycin at 41 degrees, sensitization was hardly induced, indicating a requirement for simultaneous exposure to ethanol and hyperthermia to produce a synergistic increase in bleomycin cytoxicity. A possible application of these findings to cancer treatment with bleomycin is discussed.