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

Abstract

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.