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首页> 外文期刊>Journal of Environmental Science and Health >Assessment of Ah receptor transcriptional activity mediated by halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) in human and mouse cell systems
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Assessment of Ah receptor transcriptional activity mediated by halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) in human and mouse cell systems

机译:评估人类和小鼠细胞系统中卤化的二苯并-对-二恶英和二苯并呋喃(PXDD / Fs)介导的Ah受体转录活性

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Polybrominated and mixed bromo/chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are emerging environmental contaminants of concern. Thus far, an understanding of the toxicological behavior of these chemical species and their impact upon human health is incomplete. Here we utilized human and mouse hepatocellular carcinoma cell lines to examine the ability of differentially halogenated PXDD/F congeners to induce aryl hydrocarbon receptor (AHR)-mediated transcriptional activity. Dose-response experiments in reporter cell lines identified varied potencies among differentially halogenated PXDD/F isomers by comparison of EC50 values relative to the prototypical AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Brominated PXDD/F species displayed reduced capacity to activate the mouse AHR, compared to TCDD. Only BrCl3 dibenzo-p-dioxin was found to have a greater relative potency than TCDD to induce human AHR transcriptional activity. Human cells required approximate to 10-29-fold higher ligand concentrations to induce analogous AHR activity, relative to mouse cells. Decreased sensitivity of the human AHR to brominated dibenzofuran congeners directly corresponded to the number of bromine functional groups. Mixtures of these compounds exhibited an additive effect on AHR activation. The data also support the inclusion of mixed halogenated dibenzo-p-dioxins and dibenzofurans into routine environmental screening procedures as well as more thorough toxicological characterization of PXDD/Fs.
机译:多溴和混合的溴/氯二苯并-对-二恶英和二苯并呋喃(PXDD / Fs)是令人关注的新兴环境污染物。迄今为止,对这些化学物质的毒理学行为及其对人类健康的影响的了解还不完整。在这里,我们利用人类和小鼠肝细胞癌细胞系来研究差异卤代PXDD / F同系物诱导芳基烃受体(AHR)介导的转录活性的能力。通过比较相对于原型AHR激动剂2,3,7,8-四氯二苯并-对-二恶英(TCDD)的EC50值,在报告细胞系中进行剂量反应实验,发现了差异卤代PXDD / F异构体之间的不同效力。与TCDD相比,溴化PXDD / F物种激活小鼠AHR的能力降低。发现仅BrCl3二苯并-对-二恶英具有比TCDD更高的诱导人AHR转录活性的相对效力。相对于小鼠细胞,人类细胞需要大约10-29倍的高配体浓度才能诱导类似的AHR活性。人AHR对溴化二苯并呋喃同类物的敏感性降低直接对应于溴官能团的数量。这些化合物的混合物表现出对AHR激活的加和作用。数据还支持将混合的卤代二苯并-对-二恶英和二苯并呋喃纳入常规环境筛选程序,以及对PXDD / F进行更彻底的毒理学表征。

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