Species-level differences between mice and rats in regards to micronucleus induction with the hypothermia-inducing drug haloperidol.
Species-level differences in response to micronucleus induction with haloperidol, a drug that can induce hypothermia, were investigated. Haloperidol was intraperitoneally (i.p.) administered to mice (12.5-50 mg/kg) and rats (25-100 mg/kg), and the rectal temperature was then measured. At every investigated dose, haloperidol transiently decreased the rectal temperature in mice to less than 30 degrees C. However, the rectal temperature decreased to approximately 34 degrees C in rats. For micronucleus induction, haloperidol at doses of 25 and 50 mg/kg resulted in a statistically significant increase in micronucleated polychromatic erythrocyte frequency in the 48 h sampling group of mice, but not in rats. In addition, relatively large micronuclei (diameter of micronucleus > one-fourth the diameter of the cytoplasm) accounted for 46-47% of the induced micronuclei in mice, suggesting that hypothermia affected the mitotic apparatus. Thus, hypothermia can induce micronuclei in vivo as a secondary effect, and the hypothermic response to haloperidol in mice was stronger than that of rats. Micronuclei could only be induced in mice during this study. Therefore, species-level differences may exist in regards to micronucleus induction by hypothermia-inducing drugs.
Asanami
Shougo
S
Chubu Branch, Otsuka Pharmaceutical Factory, Inc., 3-13-21 Marunouch, Naka-ku, Nagoya 460-0002, Japan. asanamis@otsuka.jp
Shimono
Kazuyuki
K
D000818:Animals; D001831:Body Temperature; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000235:genetics; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006358:Hot Temperature; D007036:Hypothermia, Induced; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced / Q000187:drug effects* / Q000706:statistics & numerical data; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D006220:Haloperidol