Evaluation of a repeated dose liver micronucleus assay in rats treated with two genotoxic hepatocarcinogens, dimethylnitrosamine and 2-acetylaminofluorene: The possibility of integrating micronucleus tests with multiple tissues into a repeated dose general toxicity study

Publication date: Available online 30 October 2014 Source:Mutation Research/Genetic Toxicology and Environmental Mutagenesis Author(s): Rie Takashima , Hironao Takasawa , Kazufumi Kawasako , Wakako Ohyama , Emiko Okada , Kazunori Narumi , Yohei Fujiishi , Yumi Wako , Katsuaki Yasunaga , Akiko Hattori , Masayoshi Kawabata , Kiyoko Nakadate , Munehiro Nakagawa , Shuichi Hamada As part of a collaborative study by the Collaborative Study Group for Micronucleus Test (CSGMT) of the Mammalian Mutagenicity Study Group (MMS) in the Japanese Environmental Mutagen Society (JEMS), the present study evaluated the effectiveness of the repeated dose liver micronucleus (RDLMN) assay. Two genotoxic hepatocarcinogens, dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2-AAF), were administered orally to male rats (6 weeks old at the initial dosing) once daily for 14 and 28 days to evaluate the micronucleus (MN) inducibility in the liver. In addition, these chemicals were evaluated for MN inducibility in the bone marrow (BM) and gastrointestinal (GI) tract, i.e. glandular stomach and colon of the same animals used in the RDLMN assay. As a result, both chemicals produced positive results in the liver, although a weak positive response was given by 2-AAF. DMN gave negative results in the tissues other than the liver. 2-AAF produced positive responses in the BM and glandular stomach, and a prominent response was particularly observed in the glandular stomach, which is directly ...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research