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 (31.3-250 mg/kg) or reserpine (500-2000 mglkg) intraperitoneally and measured temperature rectally. Chlorpromazine at 62.5-250 mg/kg and reserpine at all doses significantly decreased rectal temperature, although the hypothermic response was weaker than previously reported in mice. Only chlorpromazine at 250 mg/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 500 mg/kg were exposed to an environmental temperature of 16 degreesC for 6, 12, or 24 h to keep their body temperature under 33 degreesC, only the 24 h treatment group significantly induced micronuclei. In addition, relatively large micronuclei (diameter of micronucleus greater than or equal to 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. (C) 2000 Elsevier Science B.V. All rights reserved.