title: Evaluation of mutagenicity of acrylamide using RBC Pig-a and PIGRET assays by single peroral dose in rats.
abstract: The Pig-a gene mutation assay, a powerful tool for evaluating in vivo genotoxicity, is based on flow cytometric enumeration of red blood cells (RBCs), which are deficient in glycosylphosphatidylinositol anchored proteins caused by mutation(s) in the Pig-a gene. Various approaches for measuring cells with mutated Pig-a gene have been developed. The Pig-a assay targeting concentrated reticulocytes - the PIGRET assay - has the potential to detect genotoxicity in early stages of the study. To verify the potential and usefulness of the PIGRET assay for short-term testing, we conducted a joint research with the Mammalian Mutagenicity Study (MMS) Group of the Japanese Environmental Mutagen Society. As part of this study, we evaluated the genotoxicity of a single oral administration of acrylamide (AA) at 25, 50, 100, 137.5, and 175mg/kg using the PIGRET and Pig-a assays targeting RBCs (RBC Pig-a assay) at 7, 14, and 28 days after dosing. Toxic effects induced by AA, such as hind limb weak-paralysis, reduction of body weight gain, and reticulocytosis, were observed in AA-treated groups. However, we detected no significant increases in Pig-a mutant frequencies using either the PIGRET or RBC Pig-a assay. Therefore, we concluded that the genotoxicity of AA could not be detected by these assays under our experimental conditions.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: horibata@nihs.go.jp.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Horibata
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ukai
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012156:Reticulocytes / Q000187:drug effects*
chemical_list: D008565:Membrane Proteins; D009153:Mutagens; C080086:phosphatidylinositol glycan-class A protein; D020106:Acrylamide
keywords: Acrylamide; Glycosylphosphatidylinositol anchor; Pig-a gene; Red blood cell; Reticulocyte