title: Evaluation of the mutagenicity of alkylating agents, methylnitrosourea and temozolomide, using the rat Pig-a assay with total red blood cells or reticulocytes.
abstract: A collaborative study of the endogenous phosphatidylinositol glycan class A (Pig-a) gene mutation assay was conducted by the Japanese Environmental Mutagen Society/Mammalian Mutagenicity Study Group with a single-dosing regimen of test chemicals administered to male rats. As a part of the study, two DNA alkylating agents, methylnitrosourea (MNU) and temozolomide (TMZ), were dosed by single oral gavage at 25, 50, and 100mg/kg body weight. Pig-a mutant analysis of total red blood cells (RBCs; RBC Pig-a assay) and reticulocytes (RETs; PIGRET assay) was performed on Days 8, 15 and 29 after the administration. Both chemicals increased Pig-a mutants among RBCs and RETs with dose dependency on all days examined. The mutant frequencies were higher among RETs compared with RBCs, indicating that the PIGRET assay could detect mutagenicity more sensitively than the RBC Pig-a assay after a single dose of test chemicals.
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan. Electronic address: Muto.Shigeharu@mf.mt-pharma.co.jp.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Muto
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Ando
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwase
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Uno
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008770:Methylnitrosourea / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects*; D000077204:Temozolomide
chemical_list: D000477:Alkylating Agents; D008565:Membrane Proteins; D009153:Mutagens; C080086:phosphatidylinositol glycan-class A protein; D008770:Methylnitrosourea; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Flow cytometry; Methylnitrosourea; Phosphatidylinositol glycan complementation class A gene; Pig-a assay; Temozolomide