Micronucleus induction in rat liver and bone marrow by acute vs. repeat doses of the genotoxic hepatocarcinogen monocrotaline.

The liver micronucleus (MN) assay is useful for predicting genotoxic rodent hepatocarcinogenicity. We have recently established the repeated-dose liver MN (RDLMN) assay in rats for integration into general toxicity studies. To investigate the effectiveness of the RDLMN assay, the genotoxic rodent hepatocarcinogen, monocrotaline (MCT), was administered by oral gavage to 6-week old male rats once daily for 14 days at 0.

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.

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.