title: Evaluation of a single-dose PIGRET assay for acetaminophen in rats compared with the RBC Pig-a assay.
abstract: As a part of a collaborative study of the Pig-a assay by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society, a genotoxicity study on acetaminophen (APAP) was performed using the red blood cell (RBC) Pig-a and PIGRET assays. The dose levels were set at 0 (vehicle, 0.5% methylcellulose solution), 500, 1000, and 2000mg/kg, and APAP was administered once by oral gavage to male Sprague Dawley rats. For the positive control group, N-nitroso-N-ethylurea (ENU, 40mg/kg) was administered in the same way. The RBC Pig-a and PIGRET assays were performed using peripheral blood collected at pre-dosing and 1, 2 and 4 weeks after dosing. In both the RBC Pig-a and PIGRET assays, there were no changes in the Pig-a gene mutant frequency (MF) by the APAP treatment at any time point. The Pig-a MFs as measured by the RBC Pig-a assay for the ENU-treated group increased in a time-dependent manner with the maximum value at week 4; however, those using the PIGRET assay reached comparable values at week 1. Based on the above results, APAP was determined to have no mutagenicity under the conditions of this study, and the PIGRET assay could detect mutagenicity of ENU much earlier than the RBC Pig-a assay.
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan. Electronic address: suzuki-yuta@bozo.co.jp.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Goto
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Saratani
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takata
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan.
authors.forename: Takezo
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Gotemba Laboratory, BoZo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka 412-0039, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Okazaki
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods*; D051381:Rats; D012156:Reticulocytes / Q000187:drug effects*
chemical_list: D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D000082:Acetaminophen
keywords: Genotoxicity; Mutagenicity; Pig-a assay; Reticulocyte