Synergistic cell killing by antitumor agents and hyperthermia in cultured cells

The effects of treatment with several antitumor agents in combination with hyperthermia (42 degrees and 43 degrees) on the cell survival of cultured mouse leukemia L5178Y and mammary carcinoma FM3A cells were studied by following clonal growth in a soft-agar medium. L5178Y cells were more heat-sensitive than FM3A cells. The cytotoxicity of bleomycin was markedly increased when the cells were treated with the drug in combination with hyperthermia or were preheated prior to drug treatment. The sensitization of FM3A cells to bleomycin was much more pronounced at 43 degrees than 42 degrees. The action of adriamycin was also potentiated at the elevated temperatures, but that of daunomycin was not. The sensitization of FM3A cells to adriamycin at 43 degrees, however, was limited to short times of heat exposure; the cells becoming resistant to further killing by adriamycin after heat exposure times of more than 30 min. The two cell lines were resistant to the cytotoxic action of low concentrations of aclacinomycin A at 37 degrees, but they became sensitized at 42 degrees and 43 degrees. The cytotoxicity of actinomycin D was also markedly potentiated at 42 degrees. The cytotoxic effects of mitomycin C, neocarzinostatin, carboquone and 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) were also appreciably potentiated at 42 degrees but those of cytosine arabinoside, 5-fluorouracil and vincristine were not.