Transient hypothermia induces micronuclei in mice.
We investigated the effect of hypothermia on micronucleus induction in mouse bone marrow cells. To induce hypothermia, we administered chlorpromazine, which was negative in an in vitro chromosome aberration test, at 3.13, 6.25, 12.5, 25, 50, and 100 mg/kg intraperitoneally. Doses of 12.5-100 mg/kg decreased rectal temperature transiently to less than 33 degrees C. The temperature depression following 25-100 mg/kg lasted for 11 h before returning to normal 24 h later except for the 100 mg/kg treatment group. Doses of 25-100 mg/kg produced a statistically significant (p < 0.01) increase in micronucleated polychromatic erythrocyte frequencies 48 h after dosing. When mice that were administered chlorpromazine at 25, 50, and 100 mg/kg were exposed to an environmental temperature of 30 degrees C for 46 h to keep their body temperature within normal range, the frequency of micronucleated erythrocytes did not increase. In addition, relatively large micronuclei (diameter of micronucleus > or = 1/4 diameter of cytoplasm) accounted for 53-58% of the induced micronuclei. The results suggest that the transient hypothermia of less than 33 degrees C for 11 h induced micronuclei in bone marrow cells, and one possible mechanism was disturbance of the mitotic apparatus.
Asanami
S
S
Naruto Research Institute, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan. asanamsy@otsukakj.co.jp
Shimono
K
K
Kaneda
S
S
D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure*; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective
D002746:Chlorpromazine