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首页> 外文期刊>Environment international >Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
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Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor

机译：表征氯化，溴化和混合卤代二恶英，呋喃和联苯作为芳烃受体的强效和部分激动剂

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摘要

The Aryl hydrocarbon receptor (AhR) binds a variety of chlorinated and brominated dioxins, furans and biphenyls. Mixed halogenated variants have been recently identified in food at significant levels but full characterisation requires potency data in order to gauge their impact on risk assessment. Rat H411E and human MCF-7 cells were treated with various mixed halogenated ligands. Antagonist properties were measured by treating cells with various concentrations of TCDD in the presence of EC_(25) of the putative antagonist. Measurement of CYP1A1 RNA was used to quantify the potency of agonism and antagonism. The PXDDs were found to be slightly less potent than the corresponding fully chlorinated congeners with the exception of 2-B,3,7,8-TriCDD which was 2-fold more potent than TCDD. PXDFs and non-ortho-PXBs were found to be more potent than their chlorinated congeners whilst several mono-ortho-substituted PXBs were shown to have partial agonistic properties. REPs were produced for a range of mixed halogenated AhR-activating ligands providing a more accurate estimation of potency for risk assessment. Several environmentally abundant biphenyls were shown to be antagonists and reduce the ability of TCDD to induce CYP1A1. The demonstration of antagonism for AhR ligands represents a challenge for existing REP risk assessment schemes for AhR ligands.
机译：芳烃受体（AhR）结合多种氯化和溴化的二恶英，呋喃和联苯。最近在食品中发现了卤化混合变体的含量很高，但要全面表征，需要效力数据才能评估其对风险评估的影响。用各种混合的卤代配体处理大鼠H411E和人MCF-7细胞。通过在假定的拮抗剂EC_（25）存在下用各种浓度的TCDD处理细胞来测量拮抗剂性能。 CYP1A1 RNA的测量用于量化激动和拮抗作用的效力。发现PXDDs的效力略低于相应的完全氯化的同类物，但2-B，3,7,8-TriCDD的效力比TCDD的效力高2倍。发现PXDF和非邻位PXB比它们的氯化同源物更有效，而一些单邻位取代的PXB具有部分激动性。为一系列混合的卤代AhR活化配体制备了REP，从而提供了更准确的风险评估潜力评估。几种环境丰富的联苯被证明是拮抗剂并降低TCDD诱导CYP1A1的能力。对AhR配体的拮抗作用表明了对现有的针对AhR配体的REP风险评估方案的挑战。

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  • 来源
    《Environment international》 |2015年第3期|49-56|共8页
  • 作者

    Richard J. Wall; Alwyn Fernandes; Martin Rose; David R. Bell; Ian R. Mellor;

  • 作者单位

    School of Life Sciences, University Park University of Nottingham, Nottingham, NG7 2RD, UK;

    The Food and Environment Research Agency, Sand Hutton, York, YO41 1LZ, UK;

    The Food and Environment Research Agency, Sand Hutton, York, YO41 1LZ, UK;

    European Chemicals Agency, Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Finland;

    School of Life Sciences, University Park University of Nottingham, Nottingham, NG7 2RD, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    AhR; Aryl hydrocarbon receptor; Dioxin; Furan; PCB; TCDD; Risk assessment; CYP1A1; Potency;

    机译：AhR;芳烃受体;二恶英;呋喃;PCB;TCDD;风险评估;CYP1A1;效力;

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