Prolonged rest period enables the detection of micronucleated hepatocytes in the liver of young adult rats after a single dose of diethylnitrosamine or mitomycin C

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Keisuke ShimadaAkihiro Wakata

Abstract

A repeated-dose micronucleus assay utilizing young adult rat hepatocytes was recently developed to evaluate the genotoxicity. In this assay, accumulation of micronucleated hepatocytes (MNHEPs) induced by repeated dosing of genotoxic chemicals is considered to be a key factor in the detection of micronuclei induction. Then, we hypothesized that the period following chemical exposure enable the detection of MNHEP induction in young adult rats, namely that MNHEPs can be generated from chromosomally damaged cells and accumulate following initiation of chemical exposure until sampling. We therefore measured MNHEP induction at 2 or 4 weeks after a single oral administration of 12.5, 50, or 100mg/kg of diethylnitrosamine (DEN) or an intraperitoneal administration of 0.5, 1.0, or 2.0mg/kg of mitomycin C (MMC) to young adult rats. Results showed a statistically significant, dose-dependent increase in the numbers of MNHEPs in DEN- or MMC-treated rats, indicating that prolonged rest period following a single dose of a genotoxic chemical enables the detection of MNHEP induction in the liver of young adult rats. From these results, a single oral administration of 50mg/kg of DEN with a 2- or 4- week rest period can be used as a positive cont...Continue Reading

References

Dec 1, 1989·Mutation Research·I ClietA Cordier
May 1, 1970·Mutation Research·M A Kastenbaum, K O Bowman
Apr 26, 2003·Mutagenesis·Hannu Norppa, Ghita C-M Falck
Aug 10, 2010·Mutation Research·Manabu YasuiMasamitsu Honma
Dec 18, 2010·Mutagenesis·Takeshi MoritaMakoto Hayashi
Feb 26, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Keisuke ShimadaAkihiro Wakata
May 9, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Yoshifumi UnoHironao Takasawa

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Citations

May 11, 2018·Drug and Chemical Toxicology·Eyyüp Rencüzoğulları, Muhsin Aydın

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