Chlorpromazine-induced hypothermia in tumour-bearing mice, acute cytotoxic drug lethality and long-term survival.
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 degrees C induced by chlorpromazine. Chlorpromazine-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.
Hultborn
R
R
Department of Histology, University of Gothenburg, Sweden.
Lundgren-Eriksson
L
L
Ottosson-Lönn
S
S
Ryd
W
W
Weiss
L
L
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D007036:Hypothermia, Induced; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D009588:Nitrogen Mustard Compounds / Q000633:toxicity*; D015996:Survival Rate; D014747:Vinblastine / Q000633:toxicity*
D009588:Nitrogen Mustard Compounds; D014747:Vinblastine; D004317:Doxorubicin; D002746:Chlorpromazine