Radio-and chemotoxicity in mice during hypothermia.
BACKGROUND
The influence of hypothermia induced by chlorpromazine (10-15 mg/kg given intra-peritoneally) on the survival from radiation and chemotherapy exposure in C57B1-mice, with or without tumour inoculation, was studied.


METHODS
The mice were exposed to either whole body irradiation (8 Gy), or doxorubicin (15 or 17.5 mg/kg i.p.), or cisplatin (20 mg/kg i. p.) and followed to ensuing death. The control mice maintained a rectal temperature of 38 degres C while those receiving chlorpromazine developed moderate hypothermia of 28 degrees C or 36 degrees C, dependent on the ambient temperature.


RESULTS
Hypothermia of 28 degrees C protected the mice from radiation-induced death and acute doxorubicin toxicity, with males gaining more protection than females. The effects appeared dependent on temperature, not on chlorpromazine. Hypothermia protected the mice from acute cisplatin toxicity and increased the anti-tumour effects in both genders. Chlorpromazine itself did not cause toxicity, neither did it change the natural course of tumour progression.


CONCLUSIONS
Hypothermia of 28 degrees C induced by chlorpromazine profoundly reduces radiation, doxorubicin-and cisplatin-induced toxicity in mice with males benefiting more than females. The hypothermia itself, not the chlorpromazine, was responsible for these effects. The anti-neoplastic activity was not compromised; rather, it was enhanced, particularly for cisplatin.
Lundgren-Eriksson
L
L
Department of Radiation Sciences, Oncology, Umeå University, Sweden. lotta.lundgren.eriksson@onkologi.umu
Palm
A
A
Ryd
W
W
Warnhammar
E
E
Hultborn
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002746:Chlorpromazine / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D007036:Hypothermia, Induced / Q000009:adverse effects* / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011835:Radiation Protection; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D000970:Antineoplastic Agents; D004317:Doxorubicin; D002945:Cisplatin; D002746:Chlorpromazine