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- Title
Evaluation of in vivo genotoxicity induced by N-ethyl- N-nitrosourea, benzo[ a]pyrene, and 4-nitroquinoline-1-oxide in the Pig-a and gpt assays.
- Authors
Horibata, Katsuyoshi; Ukai, Akiko; Kimoto, Takafumi; Suzuki, Tetsuya; Kamoshita, Nagisa; Masumura, Kenichi; Nohmi, Takehiko; Honma, Masamitsu
- Abstract
The recently developed Pig-a mutation assay is based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient red blood cells caused by a forward mutation in the Pig-a gene. Because the assay can be conducted in nontransgenic animals and the mutations accumulate with repeat dosing, we believe that the Pig-a assay could be integrated into repeat-dose toxicology studies and provides an alternative to transgenic rodent (TGR) mutation assays. The capacity and characteristics of the Pig-a assay relative to TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice, we compared the in vivo genotoxicity of single oral doses of N-ethyl- N-nitrosourea (ENU, 40 mg/kg), benzo[ a]pyrene (BP, 100 and 200 mg/kg), and 4-nitroquinoline-1-oxide (4NQO, 50 mg/kg) in the Pig-a (peripheral blood) and gpt (bone marrow and liver) gene mutation assays. Pig-a assays were conducted at 2, 4, and 7 weeks after the treatment, while gpt assays were conducted on tissues collected at the 7-week terminal sacrifice. ENU increased both Pig-a and gpt mutant frequencies (MFs) at all sampling times, and BP increased MFs in both assays but the Pig-a MFs peaked at 2 weeks and then decreased. Although 4NQO increased gpt MFs in the liver, only weak, nonsignificant increases (two- or threefold above control) were detected in the bone marrow in both the Pig-a and the gpt assay. These findings suggest that further studies are needed to elucidate the kinetics of the Pig-a mutation assay in order to use it as an alternative to the TGR mutation assay. Environ. Mol. Mutagen. 54:747-754, 2013. © 2013 Wiley Periodicals, Inc.
- Subjects
GENETIC mutation; GLYCOSYLPHOSPHATIDYLINOSITOL; ERYTHROCYTES; NITROQUINOLINE oxide; NITROSOUREAS; TOXICOLOGY; BONE marrow
- Publication
Environmental & Molecular Mutagenesis, 2013, Vol 54, Issue 9, p747
- ISSN
0893-6692
- Publication type
Article
- DOI
10.1002/em.21818