使用苯丁酸氮芥对大鼠红细胞Pig-a检测法和PIGRET检测法的评估。
Evaluation of red blood cell Pig-a assay and PIGRET assay in rats using chlorambucil.
作者信息
Maeda Akihisa, Takahashi Kei, Tsuchiyama Hiromi, Oshida Keiyu
机构信息
Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
出版信息
Mutat Res Genet Toxicol Environ Mutagen. 2016 Nov 15;811:91-96. doi: 10.1016/j.mrgentox.2015.12.006. Epub 2015 Dec 29.
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.
Pig-a试验是一种评估化合物体内致突变性的新方法，有望用于检测遗传毒性。在本研究中，为了评估针对红细胞（RBCs；红细胞Pig-a试验）和网织红细胞（RETs；PIGRET试验）的Pig-a试验的性能，于第1天以10、20和40mg/kg的剂量对雄性大鼠口服给予遗传毒性剂苯丁酸氮芥，并定期检测红细胞和网织红细胞的突变频率（MFs）。在红细胞Pig-a试验中，第15天40mg/kg剂量组以及第29天20mg/kg及以上剂量组的MFs显著增加。在PIGRET试验中，第8天所有剂量组的MFs均显著增加，第15天仅20mg/kg剂量组的MFs显著增加，但第29天各治疗组的MFs均未增加。总之，大鼠的红细胞Pig-a试验和PIGRET试验对检测苯丁酸氮芥的致突变性具有足够的敏感性，且PIGRET试验比红细胞Pig-a试验能更早、更低剂量地检测到其致突变性。
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