Diethylnitrosamine genotoxicity evaluated in sprague dawley rats using pig-a mutation and reticulocyte micronucleus assays.
Diethylnitrosamine genotoxicity evaluated in sprague dawley rats using pig-a mutation and reticulocyte micronucleus assays.
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使用猪-a 突变和网织红细胞微核测定法评估斯普拉格道利大鼠的二乙基亚硝胺遗传毒性。
DOI：
10.1002/em.21862
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发表时间：
2014
影响因子：
2.8
通讯作者：
Dertinger,StephenD
中科院分区：
文献类型：
--
作者：
Avlasevich,SvetlanaL;Phonethepswath,Souk;Labash,Carson;Carlson,Kristine;Torous,DorotheaK;Cottom,John;Bemis,JeffreyC;MacGregor,JamesT;Dertinger,StephenD
Diethylnitrosamine (DEN) is a genotoxic carcinogen, butin vivoDNA‐damaging activities are not usually evident in hematopoietic cells because the short‐lived active metabolite is formed mainly in the liver. DEN therefore represented an interesting case for evaluating the performance characteristics of blood‐based endpoints of genotoxicity that have been automated using flow cytometric analysis—frequency of micronucleated reticulocytes andPig‐amutant phenotype reticulocytes (RETCD59−) and erythrocytes (RBCCD59−). Male Sprague Dawley rats were treated for 28 consecutive days with DEN at levels up to 12.5 mg/kg/day. Serial blood samples were collected and micronucleus frequencies were determined on Days 4 and 29, while RETCD59−and RBCCD59−frequencies were determined on Days 15, 29, and 42. ThePig‐aanalyses were conducted with an enrichment step based on immunomagnetic column separation to increase the statistical power of the assay. Modest but significant reductions to reticulocyte frequencies demonstrated that bone marrow was exposed to reactive intermediates. Even so, DEN did not affect micronucleus frequencies at any dose level tested. However, RETCD59−frequencies were significantly elevated in the high dose group on Day 29, and RBCCD59−were increased at this same dose level on Days 29 and 42. These results demonstrate that thePig‐aassay is sufficiently sensitive to evaluate chemicals for genotoxic potential, even in the case of a promutagen that has traditionally required direct assessment(s) of liver tissue for detection of DNA‐damage. Environ. Mol. Mutagen. 55:400–406, 2014. © 2014 Wiley Periodicals, Inc.
