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Characterization of Quinoline Yellow Dyes As Transient Aryl Hydrocarbon Receptor Agonists.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-01-20 , DOI: 10.1021/acs.chemrestox.9b00351 Patrick Tarnow 1 , Catrin Zordick 1 , Alex Bottke 1 , Berit Fischer 1 , Friederike Kühne 1 , Tewes Tralau 1 , Andreas Luch 1
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-01-20 , DOI: 10.1021/acs.chemrestox.9b00351 Patrick Tarnow 1 , Catrin Zordick 1 , Alex Bottke 1 , Berit Fischer 1 , Friederike Kühne 1 , Tewes Tralau 1 , Andreas Luch 1
Affiliation
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The aryl hydrocarbon receptor (AHR) and estrogen receptor alpha (ERα) are two ligand activated transcription factors that are targeted by a wide range of anthropogenic compounds. Crosstalk between both receptors is well established but little understood. We previously developed a dual color luciferase assay (i.e., XEER) which allows time dissolved monitoring of the activation of both receptors in situ. The system was now used in conjunction with HPLC-qTOF to identify several quinophthalone dyes as transient receptor agonists of the AHR. Altogether the approach identified three widely used dyes, that is the plastic colorant latyl yellow 3G (LY), the structurally related textile dye disperse yellow 64 (DY), and the cosmetic dye quinoline yellow (QY). The latter was the most potent agonist followed by LY and DY as confirmed by the XEER assay and CYP1A1 gene induction in MCF7 cells. In addition QY, LY, and DY also inhibited ER signaling in an AHR-dependent manner. This establishes some evidence for quinoline yellow dyes as potential disruptors of AHR/ER signaling, raising potential toxicological concern. Although none of the dyes featured any signs of genotoxicity in vitro, our data point to the need for a systematic approach when screening for substances of potential toxicological and endocrine relevance.
中文翻译：
喹啉黄染料作为瞬态芳烃受体激动剂的表征。
芳基烃受体（AHR）和雌激素受体α（ERα）是两种配体激活的转录因子，被多种人为化合物靶向。两种受体之间的串扰是公认的，但了解甚少。我们之前开发了一种双色萤光素酶测定法（即XEER），该方法可用于时间溶解监测两个受体的活化。该系统现已与HPLC-qTOF结合使用，以鉴定几种喹酞酮染料作为AHR的瞬时受体激动剂。该方法总共确定了三种广泛使用的染料，即塑料着色剂latyl yellow 3G（LY），与结构相关的纺织品染料分散黄64（DY）和化妆品染料喹啉黄（QY）。XEER分析和CYP1A1基因在MCF7细胞中的诱导证实，后者是最有效的激动剂，其次是LY和DY。此外，QY，LY和DY也以AHR依赖性方式抑制ER信号传导。这为喹啉黄色染料作为AHR / ER信号的潜在破坏者建立了一些证据，引起了潜在的毒理学关注。尽管没有一种染料具有体外遗传毒性的迹象，但我们的数据表明，在筛选具有潜在毒理学和内分泌相关性的物质时，需要一种系统的方法。
更新日期：2020-02-11
中文翻译：
喹啉黄染料作为瞬态芳烃受体激动剂的表征。
芳基烃受体（AHR）和雌激素受体α（ERα）是两种配体激活的转录因子，被多种人为化合物靶向。两种受体之间的串扰是公认的，但了解甚少。我们之前开发了一种双色萤光素酶测定法（即XEER），该方法可用于时间溶解监测两个受体的活化。该系统现已与HPLC-qTOF结合使用，以鉴定几种喹酞酮染料作为AHR的瞬时受体激动剂。该方法总共确定了三种广泛使用的染料，即塑料着色剂latyl yellow 3G（LY），与结构相关的纺织品染料分散黄64（DY）和化妆品染料喹啉黄（QY）。XEER分析和CYP1A1基因在MCF7细胞中的诱导证实，后者是最有效的激动剂，其次是LY和DY。此外，QY，LY和DY也以AHR依赖性方式抑制ER信号传导。这为喹啉黄色染料作为AHR / ER信号的潜在破坏者建立了一些证据，引起了潜在的毒理学关注。尽管没有一种染料具有体外遗传毒性的迹象，但我们的数据表明，在筛选具有潜在毒理学和内分泌相关性的物质时，需要一种系统的方法。
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