Chlorpromazine-Induced Hypothermia in Tumour-Bearing Mice, Acute Cytotoxic Drug Lethality and Long-Term Survival

Abstract

The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28°C induced by chlorpromazine. Chlorpro-mazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity.