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首页> 外文期刊>Environmental Science & Technology >Genotoxicity Assessment of Drinking Water Disinfection Byproducts by DNA Damage and Repair Pathway Profiling Analysis
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Genotoxicity Assessment of Drinking Water Disinfection Byproducts by DNA Damage and Repair Pathway Profiling Analysis

机译:DNA损伤和修复途径分析法对饮用水消毒副产物的遗传毒性评估

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摘要

Genotoxicity is considered a major concern for drinking water disinfection byproducts (DBPs). Of over 700 DBPs identified to date, only a small number has been assessed with limited information for DBP genotoxicity mechanism(s). In this study, we evaluated genotoxicity of 20 regulated and unregulated DBPs applying a quantitative toxicogenomics approach. We used GFP-fused yeast strains that examine protein expression profiling of 38 proteins indicative of all known DNA damage and repair pathways. The toxicogenomics assay detected genotoxicity potential of these DBPs that is consistent with conventional genotoxicity assays end points. Furthermore, the high-resolution, real-time pathway activation and protein expression profiling, in combination with clustering analysis, revealed molecular level details in the genotoxicity mechanisms among different DBPs and enabled classification of DBPs based on their distinct DNA damage effects and repair mechanisms. Oxidative DNA damage and base alkylation were confirmed to be the main molecular mechanisms of DBP genotoxicity. Initial exploration of QSAR modeling using moleular genotoxicity end points (PELI) suggested that genotoxicity of DBPs in this study was correlated with topological and quantum chemical descriptors. This study presents a toxicogenomics-based assay for fast and efficient mechanistic genotoxicity screening and assessment of a large number of DBPs. The results help to fill in the knowledge gap in the understanding of the molecular mechanisms of DBP genotoxicity.
机译:遗传毒性被认为是饮用水消毒副产物(DBP)的主要问题。迄今为止,在鉴定出的700多种DBP中,只有极少数的DBP遗传毒性机制信息被评估。在这项研究中,我们使用定量毒理基因组学方法评估了20种受管制和不受管制的DBP的遗传毒性。我们使用GFP融合酵母菌株检查38种蛋白质的蛋白表达谱,这些蛋白表明所有已知的DNA损伤和修复途径。毒物基因组学测定法检测到了这些DBP的潜在遗传毒性,这与传统的遗传毒性测定法终点一致。此外,高分辨率,实时途径激活和蛋白质表达谱分析与聚类分析相结合,揭示了不同DBP之间遗传毒性机制中的分子水平细节,并基于其独特的DNA损伤作用和修复机制对DBP进行了分类。氧化性DNA损伤和碱基烷基化被证实是DBP遗传毒性的主要分子机制。使用分子遗传毒性终点(PELI)对QSAR建模的初步探索表明,本研究中DBP的遗传毒性与拓扑和量子化学描述符相关。这项研究提出了一种基于毒理基因组学的测定方法,可用于快速有效的机械遗传毒性筛查和评估大量DBP。结果有助于填补对DBP遗传毒性分子机制的了解中的知识空白。

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  • 来源
    《Environmental Science & Technology》 |2018年第11期|6565-6575|共11页
  • 作者单位

    Department of Civil and Environmental Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States,Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China;

    Department of Civil and Environmental Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States;

    Department of Civil and Environmental Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States;

    Department of Civil and Environmental Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States;

    Safe Global Water Institute and Department of Crop Sciences, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States;

    Department of Civil and Environmental Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States;

    Department of Civil and Environmental Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States,School of Civil and Environmental Engineering, Cornell University, Ithaca, New York 14850, United States;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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