Flow cytometric analysis of Pig-a gene mutation and chromosomal damage induced by procarbazine hydrochloride in CD-1 mice.
Flow cytometric analysis of Pig-a gene mutation and chromosomal damage induced by procarbazine hydrochloride in CD-1 mice.
复制标题
流式细胞术分析盐酸丙卡巴肼诱导 CD-1 小鼠 Pig-a 基因突变和染色体损伤。
DOI：
10.1002/em.21758
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发表时间：
2013
影响因子：
2.8
通讯作者：
Dertinger,StephenD
中科院分区：
文献类型：
--
作者：
Phonethepswath,Souk;Avlasevich,SvetlanaL;Torous,DorotheaK;Mereness,Jared;Bemis,JeffreyC;Macgregor,JamesT;Dertinger,StephenD
丙卡嗪是一种基因毒性致癌物，其DNA损伤活性在体外不能可靠地检测到。我们使用多终点研究设计评估了丙卡嗪对雄性CD‐1小鼠造血细胞的体内遗传毒性作用，该研究设计对微核网状细胞（MN‐RET）频率和基因突变进行了评分。用丙卡嗪治疗CD‐1小鼠3天，剂量为150 mg/kg/天。第3天采集的血液样本显示MN‐ret的强诱导作用，高剂量组平均增加29倍。治疗开始后15天和30天采集的血液用双重标记方法分析猪‐突变，这种方法便于在总红细胞和网状红细胞亚群中测量突变细胞频率。到第15天，丙卡嗪显著增加突变的网状细胞频率。突变的红细胞反应也很明显，高剂量组在第30天达到峰值。这些结果表明，在完整的动物模型中，丙卡嗪的复杂代谢和由此产生的遗传毒性得到了最好的评估，并表明所采用的流式细胞术方法提供了一种有效监测体内染色体损伤和突变的手段。环绕。中国生物工程学报，2014,34(4):544 - 544。©2013 Wiley期刊公司
Procarbazine is a genotoxic carcinogen whose DNA‐damaging activities are not reliably detected in vitro. We evaluated the in vivo genotoxic effects of procarbazine on hematopoietic cells of male CD‐1 mice using a multi‐endpoint study design that scored micronucleated reticulocyte (MN‐RET) frequency and gene mutation at thePig‐alocus. CD‐1 mice were treated for 3 days with procarbazine, up to 150 mg/kg/day. Blood samples collected on Day 3 exhibited robust induction of MN‐RETs, with the high dose group exhibiting a mean 29‐fold increase. Blood collected 15 and 30 days after treatment began was analyzed forPig‐amutation with a dual labeling method that facilitated mutant cell frequency measurements in both total erythrocytes and the reticulocyte subpopulation. Procarbazine significantly increased mutant reticulocyte frequencies by Day 15. Mutant erythrocyte responses were also apparent, with a peak incidence observed for the high dose group on Day 30. These results demonstrate that the complex metabolism and resulting genotoxicity of procarbazine is best evaluated in intact animal models, and show that the flow cytometric methods employed offer a means to efficiently monitor both in vivo chromosomal damage and mutation. Environ. Mol. Mutagen. 54:294–298, 2013. © 2013 Wiley Periodicals, Inc.