title: Gender differences in the liver micronucleus test in rats with partial hepatectomy.
abstract: The liver micronucleus test in rats with partial hepatectomy is a useful method to detect pro-clastogens such as diethylnitrosamine, the active metabolites of which do not reach the bone marrow due to their short lifespan. We have already reported that structural or numerical chromosome aberration inducers should be given before or after partial hepatectomy, respectively, to detect genotoxicity in the liver of rats. In the present study, we found that the percentage of binucleated cells in the liver from naive male rats is approximately 60% of that in female rats, which suggests a gender difference in the response to chromosome aberration inducers. Therefore, we investigated the responses to structural chromosome aberration inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and numerical chromosome aberration inducers (colchicine and carbendazim) in male and female rats. The chemicals were given to 8-week-old male and female F344 rats a day before or after partial hepatectomy and hepatocytes were isolated 4 days after the partial hepatectomy. As the results, diethylnitrosamine and 1,2-dimethylhydrazine produced a significant increase in the frequency of micronucleated hepatocytes in both genders and the responses were comparable. In the case of colchicine and carbendazim, higher frequencies in the micronucleated hepatocytes were obtained in males than in females. Taken together, the response to chromosome aberration inducers in male rats was equal to or stronger than that in female rats. It seems that the use of only male rats in the liver micronucleus test is sufficient, unless existing data indicate a toxicologically meaningful gender difference in rats.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Horikoshi 717, Fukuroi-shi, Shizuoka 437-0065, Japan. itoh.satoru.n5@daiichisankyo.co.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Itoh
authors.forename: Chiharu
authors.initials: C
authors.lastname: Hattori
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nagata
authors.forename: Wataru
authors.initials: W
authors.lastname: Takasaki
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity; D002219:Carbamates / Q000633:toxicity; D003078:Colchicine / Q000633:toxicity; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D005783:Gender Identity; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D009153:Mutagens; D004052:Diethylnitrosamine; C006698:carbendazim; D019813:1,2-Dimethylhydrazine; D003078:Colchicine