title: Evaluation of a single-dose PIGRET assay for cisplatin 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 cisplatin was performed using red blood cell (RBC) Pig-a and PIGRET assays. The dose levels were set at 0 (vehicle, physiological saline), 0.5, 1, and 2 mg/kg, and cisplatin was administered intravenously once to male F344 rats. 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 the RBC Pig-a assay, an increase in the Pig-a mutant frequency (MF) was observed at week 4 in the high dose group. Although a significant increase in the Pig-a MF was also observed at week 2 in all cisplatin-treated groups, it was considered that this change was caused by a low MF in the vehicle control group and not to be biologically relevant. In the PIGRET assay, the Pig-a MF was increased at weeks 1, 2 and 4 in the high dose group. In addition, the means of the vehicle control group's Pig-a MFs in the PIGRET assay were lower than those in the RBC Pig-a assay. Based on the above results, cisplatin was determined to have mutagenicity under the conditions of this study, and it was demonstrated that the PIGRET assay was an appropriate tool to evaluate the in vivo mutagenicity 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: D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; 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; D002945:Cisplatin
keywords: Genotoxicity; Mutagenicity; Pig-a assay;; Reticulocyte