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Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish (Danio rerio) Is Prone to Aromatic Substituent Changes

机译:斑马鱼生命早期溴化偶氮染料的毒代动力学很容易发生芳香取代基变化

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摘要

Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (Danio rerio). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQOI as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis- induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.
机译:溴偶氮染料(BADs)已被确定为日托粉尘中主要的室内溴化污染物。因此,他们对儿童的潜在健康风险值得关注。但是,BADs的毒性仍然难以捉摸。在这项研究中,在斑马鱼的胚胎中研究了两种主要的BADs,分散蓝373(DB373)和分散紫93(DV93)及其可疑的代谢物2-溴-4,6-二硝基苯胺(BDNA)的毒代动力学。 )。 DV93在120 hpf下的生物富集系数比DB373低6.2倍。非目标分析显示,尽管结构相似,但通过将亚硝基还原为亚硝基(DB373)或胺(DV93),DB373和DV93之间存在明显的代谢途径。 NAD(P)H醌氧化还原酶1(NQO1)和丙酮酸脱氢酶被预测为负责通过关联代谢产物的时间过程和酶发展来减少DB373和DV93的酶。进一步的体外重组酶和体内抑制结果证实NQOI是特异性还原DB373而不是DV93的酶。全球蛋白质组图谱分析显示,所有三种BAD均显着上调了“细胞凋亡诱导的DNA片段化”途径中蛋白质的表达水平,从而支持了BAD对诱变性芳族胺的生物活化作用。这项研究发现了BADs通过不同的真核生物酶的生物激活,这暗示了其潜在的健康风险。

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  • 来源
    《Environmental Science & Technology》 |2020年第7期|4421-4431|共11页
  • 作者单位

    Department of Chemistry University of Toronto Toronto ON M5S 3H6 Canada;

    Department of Chemistry and School of the Environment University of Toronto Toronto ON M5S 3H6 Canada;

    The Donnelly Centre University of Toronto Toronto ON M5S 3E1 Canada;

    Department of Environmental Toxicology National Institute of Environmental Health Chinese Center for Disease Control and Prevention Beijing 100021 China;

    Department of Plant Protection College of Food and Agriculture Sciences King Saud University Riyadh 11451 Saudi Arabia;

    Toxicology Centre University of Saskatchewan Saskatoon SK S7N 563 Canada;

    The Donnelly Centre and Department of Molecular Genetics University of Toronto Toronto ON M5S 3E1 Canada;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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  • 入库时间 2022-08-18 05:27:33

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