Detection of micronuclei in hepatocytes isolated from young adult rats repeatedly treated with N-nitrosodi-n-propylamine

Publication date: March 2015 Source:Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Volumes 780–781 Author(s): Yukari Terashima , Ryohei Yokoi , Ikuro Takakura , Erika Saitou , Yumi Wako , Kazufumi Kawasako , Shinji Souma , Toru Tamura To assess the effectiveness of the multiple dose liver micronucleus (MN) assay, the induction of micronuclei by N-nitrosodi-n-propylamine (NDPA), a genotoxic rodent carcinogen, was compared in hepatocytes (HEPs) and bone marrow (BM) cells. Young adult male rats were treated orally with NDPA at 6 weeks of age for 14 days using daily doses of 10, 20 and 40mg/kg. Samples of the liver and BM tissues were harvested from each animal one day following the last treatment with NDPA and were evaluated for the frequencies of micronucleated cells. Repeated doses with 40mg/kg/day of NDPA caused systemic and hepatic toxicity, including suppressed body weight gains and histopathological hepatic lesions. The frequencies of micronucleated HEPs were significantly increased in all the NDPA-treated groups in a dose-dependent manner. In contrast, the induction of micronuclei in the BM was undetectable, even at the high dose level of 40mg/kg, for which the inhibition of hematopoiesis was observed. For the detection of micronucleated HEPs induced by NDPA treatment, a 14-day administration period is adequate. The liver MN assay using naive young adult rats may be integrated into general repeated-dose toxicity studies including histopa...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research