title: Repeated dose liver micronucleus assay using clofibrate in young adult rats.
abstract: The repeated-dose liver micronucleus (MN) assay is a newly established in vivo genotoxicity test for evaluation of liver carcinogens. It may be integrated into general toxicity studies, thereby reducing the numbers of animals required for assessment of chemical safety. A collaborative study by the Mammalian Mutagenicity Study (MMS) Group further evaluated this assay using a wide range of chemicals, including carcinogens and non-carcinogens in young adult rats. In this study, we administered clofibrate (125, 250, or 500mg/kg/day) for 14 or 28 days, and examined the micronucleated (MNed) cell frequencies in the liver and bone marrow. Clofibrate is a known liver carcinogen specific to rodents and has been shown to yield negative results in many in vitro genotoxicity and carcinogenicity tests in monkeys. Clofibrate is categorized as a Group 3 chemical by the International Agency for Research on Cancer and is considered a non-genotoxic carcinogen. After treatment with clofibrate for 14 or 28 days, frequencies of hepatic MNed cells were significantly increased, but there were no differences in the ratios of hepatic M-phase cells. Clofibrate did not increase the frequency of MNed cells in the bone marrow in the 14-day study, whereas a slight increase was observed at the highest dose in the 28-day study. These results suggested that the repeated-dose liver MN assay is more sensitive to clofibrate, an indirect liver carcinogen in rodents, than the conventional bone marrow MN assay.
authors.affiliation: Suntory Business Expert Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan. Electronic address: Tomomi_Takayanagi@suntory.co.jp.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Takayanagi
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Takashima
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Wako
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kawasako
authors.affiliation: Suntory Business Expert Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Suntory Business Expert Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Hori
authors.affiliation: Suntory Business Expert Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujii
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology*; D020552:Comet Assay; D003299:Cooperative Behavior; D004334:Drug Administration Schedule; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012957:Societies, Pharmaceutical
chemical_list: D000960:Hypolipidemic Agents; D002994:Clofibrate
keywords: Clofibrate; Liver; Micronucleus assay; Repeated-dose study