title: Evaluation of the repeated-dose liver micronucleus assay with p-dimethylaminoazobenzene.
abstract: The micronucleus induction by p-dimethylaminoazobenzene (DAB), a genotoxic rat liver carcinogen, was assessed in the liver and bone marrow of young adult rats after the repeated administration of DAB for 14 (Lab. 1) and 28 (Lab. 2) days. Three dose levels, 25, 50 and 100mg/kg/day, were used for the investigations in both labs. The frequency of micronucleated hepatocytes was significantly increased in a dose-dependent manner after the repeated administration of DAB at 50mg/kg/day or more for 14 and 28 days. Similarly, the frequency of micronucleated immature erythrocytes in the bone marrow was increased after the repeated administration of DAB at 100mg/kg/day for 14 and 28 days. These results indicate that the repeated-dose liver micronucleus assay allowed for the detection of micronucleus induction by DAB, and that the lowest detectable dose for micronucleus induction in the liver was lower than in the bone marrow. Thus, the repeated-dose liver micronucleus assay using young adult rats is considered suitable for the detection of micronucleus induction by liver carcinogens, such as DAB.
authors.affiliation: Central Research Laboratories (Lab. 1), Hokko Chemical Industry Co. Ltd., 2165 Toda, Atsugi-shi, Kanagawa 243-0023, Japan. Electronic address: shimada-y@hokkochem.co.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Hatano Research Institute, Food and Drug Safety Center (Lab. 2), 729-5 Ochiai, Hadano-shi, Kanagawa 257-8523, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sui
authors.affiliation: LSI Medience Corporation, 14 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Wako
authors.affiliation: LSI Medience Corporation, 14 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kawasako
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D003299:Cooperative Behavior; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects; D012957:Societies, Pharmaceutical; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D004124:p-Dimethylaminoazobenzene
keywords: Integration; Liver micronucleus assay; Micronucleus induction; Repeated-dose toxicity study; Young adult rat; p-Dimethylaminoazobenzene (DAB)