INTERACTION OF THERMAL TOLERANCE WITH DRUG CYTOTOXICITY INVITRO

The effect of preheating EMT6 [mouse mammary tumor] cells in vitro on their response to cytotoxic agents at either 43.degree. C or 37.degree. C was investigated. Preheating for 3 h at 40.degree. C produced measurable protection (thermal tolerance) to subsequent treatment for 1 h at 43.degree. C. This preheat treatment reduced cell killing by BLM [bleomycin] and BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] (drug tolerance) present during 1 h at 43.degree. C. In contrast, no such heat-induced drug tolerance was seen with ADR [adriamycin]. An additional effect with ADR was the apparent elimination of heat-induced thermal tolerance at toxic drug doses. However, preheating under these conditions had no effect on the subsequent cytotoxicity of any of these drugs at 37.degree. C. Also, preheating for 1 h at 43.degree. C was found to sensitize cells to BLM and BCNU toxicity at 37.degree. C but to protect against ADR toxicity. The results are discussed in relation to known mechanisms of cell killing by heat and of thermal tolerance.