title: Evaluation of red blood cell Pig-a assay and PIGRET assay in rats using chlorambucil.
abstract: The Pig-a assay is a novel method to assess the in vivo mutagenicity of compounds, and it is expected to be useful for the detection of genotoxicity. In this study, to assess the performance of the Pig-a assay targeting red blood cells (RBCs; RBC Pig-a assay) and reticulocytes (RETs; PIGRET assay), chlorambucil, which is a genotoxicant, was orally administered to male rats once at 10, 20 and 40mg/kg on Day 1, and the mutant frequencies (MFs) of RBCs and RETs were examined periodically. In the RBC Pig-a assay, significant increases in MFs were observed at 40mg/kg on Day 15 and at 20mg/kg or higher on Day 29. In the PIGRET assay, MFs increased significantly at all dose levels on Day 8 and only at 20mg/kg on Day 15, but there was no increase in MFs in the treatment groups on Day 29. In conclusion, the RBC Pig-a assay and PIGRET assay in rats have sufficient sensitivity to detect the mutagenicity of chlorambucil, and the PIGRET assay could detect its mutagenicity earlier and at a lower dose than the RBC Pig-a assay.
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Akihisa_Maeda@nts.toray.co.jp.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tsuchiyama
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Keiyu
authors.initials: K
authors.lastname: Oshida
mesh_terms: D000818:Animals; D002699:Chlorambucil / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects*
chemical_list: D008565:Membrane Proteins; D009153:Mutagens; C080086:phosphatidylinositol glycan-class A protein; D002699:Chlorambucil
keywords: Chlorambucil; PIGRET assay; Pig-a assay; Rat; Single dose