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Temperature Dependence of Adriamycin, cis-Diamminedichloroplatinum, Bleomycin, and 1,3-Bis(2-chloroethyl)-1-nitrosourea Cytotoxicity in Vitro¹

Department of Internal Medicine, Veterans Administration Medical Center, Tucson, Ariz, and 300 East Roosevelt Rd., Little Rock, AR 72206

² To whom requests for reprints should be addressed, at the Section of Hematology/Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Ark. 72205.

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.

¹ This investigation was supported in part by USPHS Grant Ca 32154 awarded by the National Cancer Institute, Department of Health and Human Services, and Veterans Administration Merit Review funding.

Received 5/28/82. Accepted 11/ 4/82.

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