Effects of chemically- and environmentally-induced hypothermia on micronucleus induction in rats.
We investigated micronucleus induction in rats treated with chlorpromazine and reserpine, drugs that induce hypothermia. We administered chlorpromazine (31.3--250mg/kg) or reserpine (500--2000 mg/kg) intraperitoneally and measured temperature rectally. Chlorpromazine at 62.5-250mg/kg and reserpine at all doses significantly decreased rectal temperature, although the hypothermic response was weaker than previously reported in mice. Only chlorpromazine at 250mg/kg decreased rectal temperature transiently to <33 degrees C for 20h and induced a statistically significant increase in micronucleated polychromatic erythrocyte frequency. When rats treated with reserpine at 500mg/kg were exposed to an environmental temperature of 16 degrees C for 6, 12, or 24h to keep their body temperature under 33 degrees C, only the 24h treatment group significantly induced micronuclei. In addition, relatively large micronuclei (diameter of micronucleus> or = 1/4 diameter of cytoplasm) accounted for 33.0% of the induced micronuclei, suggesting that hypothermia affected the mitotic apparatus. The hypothermic response to chlorpromazine and reserpine was weaker in rats than in mice, and it was correspondingly more difficult to induce micronuclei in rats with those drugs.
Asanami
S
S
Naruto Research Institute, Otsuka Pharmaceutical Factory, 115 Muya-cho, Naruto, Tokushima 772-8601, Japan. asanamsy@otsukakj.co.jp
Shimono
K
K
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D002746:Chlorpromazine / Q000008:administration & dosage / Q000633:toxicity; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D007036:Hypothermia, Induced; D007274:Injections, Intraperitoneal; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000502:physiology*; D015162:Micronucleus Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors
D012110:Reserpine; D002746:Chlorpromazine