Temperature Dependence of Adriamycin, cis-Diamminedichloroplatinum Bleomycin, and 1,3-Bis(2-chloroethyl)-1-nitrosourea Cytotoxicity in Vitro’

We have examined the effect of mildly hypothermic temperatures (22-32°) on the cytotoxicity of Adriamycin, cis-diamminedichloroplatinum, bleomycin, and 1,3-bis(2-chloroethyl)-1-nitrosourea in Chinese hamster ovary cells in vitro. Over a dose range of Adriamycin, cell killing at 30° was reduced by 1 to 3 orders of magnitude as compared to that at 37°. cis-Diamminedichloroplatinum was also less cytotoxic at 30° (0.4 to 1.2 orders of magnitude) than at 37°. For bleomycin and 1,3-bis(2-chloroethyl)-1-nitrosourea, the reduction in cytotoxicity at 30° in comparison to 37° was less marked. All drugs were more toxic at 42.4-43° than at 37°. Precooling of cells for 2 hr at 30° did not alter the cell killing caused by these drugs at elevated temperatures. These results suggest that a more selective anticancer effect might result if some chemotherapeutic drugs were administered during whole-body hypothermia and regional-local hyperthermia of tumor masses.