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Evaluation of red blood cell Pig-a assay and PIGRET assay in rats using chlorambucil.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ( IF 2.3 ) Pub Date : 2016 Nov 15 , DOI: 10.1016/j.mrgentox.2015.12.006
Akihisa Maeda 1 , Kei Takahashi 1 , Hiromi Tsuchiyama 1 , Keiyu Oshida 1
Affiliation  

The Pig-a assay is a novel method to assess the in vivo mutagenicity of compounds, and it is expected to be useful for the detection of genotoxicity. In this study, to assess the performance of the Pig-a assay targeting red blood cells (RBCs; RBC Pig-a assay) and reticulocytes (RETs; PIGRET assay), chlorambucil, which is a genotoxicant, was orally administered to male rats once at 10, 20 and 40mg/kg on Day 1, and the mutant frequencies (MFs) of RBCs and RETs were examined periodically. In the RBC Pig-a assay, significant increases in MFs were observed at 40mg/kg on Day 15 and at 20mg/kg or higher on Day 29. In the PIGRET assay, MFs increased significantly at all dose levels on Day 8 and only at 20mg/kg on Day 15, but there was no increase in MFs in the treatment groups on Day 29. In conclusion, the RBC Pig-a assay and PIGRET assay in rats have sufficient sensitivity to detect the mutagenicity of chlorambucil, and the PIGRET assay could detect its mutagenicity earlier and at a lower dose than the RBC Pig-a assay.

中文翻译:

使用苯丁酸氮芥对​​大鼠红细胞 Pig-a 测定和 PIGRET 测定的评价。

Pig-a试验是一种评估化合物体内致突变性的新方法,有望用于检测基因毒性。在本研究中,为了评估针对红细胞(RBCs;RBC Pig-a 试验)和网织红细胞(RETs;PIGRET 试验)的 Pig-a 试验的性能,苯丁酸氮芥是一种基因毒物,曾对雄性大鼠口服一次在第 1 天以 10、20 和 40mg/kg 给药,并定期检查 RBC 和 RET 的突变频率 (MF)。在 RBC Pig-a 试验中,第 15 天 40mg/kg 和第 29 天 20mg/kg 或更高时观察到 MF 显着增加。在 PIGRET 试验中,第 8 天所有剂量水平的 MF 显着增加,仅第 15 天为 20mg/kg,但第 29 天治疗组的 MF 没有增加。 总之,
更新日期:2017-01-31
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