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Evaluation of the mutagenicity of alkylating agents, methylnitrosourea and temozolomide, using the rat Pig-a assay with total red blood cells or reticulocytes.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2016 Nov 15 , DOI: 10.1016/j.mrgentox.2016.01.010
Shigeharu Muto 1 , Katsuya Yamada 1 , Tatsuya Kato 1 , Masamitsu Ando 1 , Yoshimi Inoue 1 , Yumiko Iwase 1 , Yoshifumi Uno 1
Affiliation  

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.

中文翻译:

使用总红细胞或网织红细胞的大鼠 Pig-a 试验评估烷化剂、甲基亚硝基脲和替莫唑胺的致突变性。

日本环境诱变剂协会/哺乳动物致突变性研究小组对内源性磷脂酰肌醇聚糖 A 类 (Pig-a) 基因突变试验进行了一项合作研究,对雄性大鼠采用单次给药试验化学品方案。作为研究的一部分,两种 DNA 烷化剂,甲基亚硝基脲 (MNU) 和替莫唑胺 (TMZ),以 25、50 和 100 毫克/千克体重通过单次口服管饲给药。在给药后第 8、15 和 29 天进行总红细胞(RBC;RBC Pig-a 测定)和网织红细胞(RET;PIGRET 测定)的 Pig-a 突变分析。两种化学物质都增加了 RBCs 和 RETs 中的 Pig-a 突变体,并且在检查的所有天数中具有剂量依赖性。与 RBC 相比,RET 的突变频率更高,
更新日期:2017-01-31
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