The in vivo Pig-a gene mutation assay is useful for evaluating the genotoxicity of ionizing radiation in mice
The in vivo Pig-a gene mutation assay is useful for evaluating the genotoxicity of ionizing radiation in mice
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DOI：
10.1002/em.21724
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发表时间：
2012-10-01
影响因子：
2.8
通讯作者：
Kunugita, Naoki
中科院分区：
文献类型：
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作者：
Ohtani, Shin;Unno, Aiko;Kunugita, Naoki
体内Pig-a突变试验已适用于测量大鼠、小鼠、猴和人的突变。迄今为止，该试验主要用于评估已知为强效点诱变剂的化学品的致突变性。该分析尚未用于测量与电离辐射相关的生物效应。在本研究中，我们改良了Pig-a基因突变测定法（Kimoto et al. [2011 b]：Mutat Res 723：36-42），并使用荧光标记的抗CD 24、抗TER-119和抗CD 71进行3色染色，以检测X射线照射小鼠的总红细胞（RBC）和网织红细胞（RET）中的Pig-a突变频率。单次暴露于X射线照射导致Pig-a突变频率的剂量和时间依赖性增加，并且这些随后随着时间的推移而下降，返回到背景频率。相同总量的辐射，以单次剂量或以每周间隔四次重复剂量的形式递送，将Pig-a突变频率增加到相当的水平，在单次剂量后23周或最后一次重复剂量后23周达到最大值。这些增加的频率随后恢复到背景水平。我们的结果表明，三色Pig-a试验是有用的，在体内辐射的遗传毒性评价。Environ.摩尔诱变剂，2012. (c)2012 Wiley Periodicals，Inc.
The in vivo Pig-a mutation assay has been adapted for measuring mutation in rats, mice, monkeys, and humans. To date, the assay has been used mainly to assess the mutagenicity of chemicals that are known to be powerful point mutagens. The assay has not been used to measure the biological effects associated with ionizing radiation. In this study, we modified the Pig-a gene mutation assay (Kimoto et al. [2011b]: Mutat Res 723:36-42) and used 3-color staining with fluorescently labeled anti-CD24, anti-TER-119, and anti-CD71 to detect the Pig-a mutant frequencies in total red blood cells (RBCs) and in reticulocytes (RETs) from X-irradiated mice. Single exposures to X-irradiation resulted in dose- and time-dependent increases in Pig-a mutant frequencies, and these subsequently declined over time returning to background frequencies. The same total amount of radiation, delivered either as a single dose or as four repeat doses at weekly intervals, increased Pig-a mutant frequencies to comparable levels, reaching maxima 23 weeks after the single dose or 23 weeks after the last of the repeat doses. These increased frequencies subsequently returned to background levels. Our results indicated that the 3-color Pig-a assay was useful for evaluating the in vivo genotoxicity of radiation. Environ. Mol. Mutagen., 2012. (c) 2012 Wiley Periodicals, Inc.