Brominated dioxin-like compounds: in vitro assessment in comparison to classical dioxin-like compounds and other polyaromatic compounds
Brominated dioxin-like compounds: in vitro assessment in comparison to classical dioxin-like compounds and other polyaromatic compounds
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DOI：
10.1016/s0160-4120(03)00105-3
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发表时间：
2003-09-01
影响因子：
11.8
通讯作者：
Sakai, S
中科院分区：
文献类型：
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作者：
Behnisch, PA;Hosoe, K;Sakai, S
最近，一些国家同意通过《关于持久性有机污染物的斯德哥尔摩公约》。今后的一项义务将是在获得新的证据时增加其他持久性有机污染物。体外细胞生物测定提供了一种快速、灵敏、相对便宜的方法来筛选可能的POP候选物。在本研究中，我们利用Micro-EROD（乙氧基-间苯二酚-o -去乙基化酶）和DR-CALUX（二恶英反应性化学激活荧光素酶基因表达）这两种最先进的生物测定方法，研究了几种二恶英样持久性有机污染物的芳烃（Ah）受体活性。在我们的研究中使用的Micro-EROD系统使用野生型大鼠肝细胞系（大鼠肝H4IIEC3/T细胞），而DR-CALUX生物测定由转基因大鼠肝癌H4IIE细胞系组成，该细胞系将萤火虫荧光素酶基因偶联二恶英反应元件（DREs）作为报告基因。在DR-CALUX生物测定中，我们使用了24小时的暴露时间，而在Micro-EROD生物测定中我们使用了72小时的暴露时间。本研究的目的是比较传统的类二恶英持久性有机污染物（如多氯二苯并二恶英和呋喃，PCDD/Fs和共面多氯联苯，PCBs）与未来可能添加到当前毒性等效因子（TEF）模型中的其他几种可能的候选者。因此，本研究比较了体外CYP1A1 （Micro-EROD生物测定）和萤火虫荧光素酶诱导（DR-CALUX生物测定）对几种混合多卤二苯并二苯并-呋喃（PXDD/Fs； X=Br， Cl或F）、烷基取代多卤二苯并-呋喃（PMCDD/Fs; M =甲基）、多卤联苯（PXBs， X=Br, Cl）、多溴联苯醚（PBDEs）、五溴苯酚（PBPs）和四溴双酚a （TBBP-A）的影响。我们还评估了这些化合物的同源特异性相对效力（REPs）和效力（TCDDmax的%），并讨论了这些化合物的剂量-反应曲线，以及其他几种ah受体激动剂的类二恶英效力，如多芳烃（PAHs）和多氯萘（PCNs）。几种PXDD/F同系物的REP值最高，其次是共面pxb、三氯PCDD/F、PAHs、PBDE-126、1-6-HxCN和一些溴化阻燃剂（TBBP-A）。这些体外研究表明，有必要进一步研究更多的ah受体激动剂的二恶英样效力。(C) 2003 Elsevier Ltd.版权所有。
Recently, several countries agreed to adopt the Stockholm convention on persistent organic pollutants (POPs). One future obligation will be to add other POPs as new evidence becomes available. In vitro cell-based bioassays offer a rapid, sensitive, and relatively inexpensive solution to screen possible POP candidates. In the present study, we investigated the aryl hydrocarbon (Ah)-receptor activity of several dioxin-like POPs by using the Micro-EROD (Ethoxy-Resorufin-O-Deethylase) and DR-CALUX (Dioxin-Responsive-Chemical Activated Luciferase gene expression) bioassays, which are two state-of-the-art methods. The Micro-EROD system used in our study utilizes a wildtype rat liver cell line (rat liver H4IIEC3/T cells), while the DR-CALUX bioassay consists of a genetically modified rat hepatoma H4IIE cell line that incorporates the firefly luciferase gene coupled to dioxin-responsive elements (DREs) as a reporter gene. In the case of the DR-CALUX bioassay, we used an exposure time of 24 h, whereas we used a 72-h exposure time in the Micro-EROD bioassay. The aim of this study was to compare conventional dioxin-like POPs (such as polychlorinated dibenzodioxins and -furans, PCDD/Fs and coplanar polychlorinated biphenyls, PCBs) with several other classes of possible candidates to be added to the current toxicity equivalent factor (TEF) model in the future. Therefore, this study compares in vitro CYP1A1 (Micro-EROD bioassay) and firefly luciferase induction (DR-CALUX bioassay) in several mixed polyhalogenated dibenzodioxins and -furans (PXDD/Fs; X=Br, Cl, or F), alkyl-substituted polyhalogenated dibenzodioxins and -furans (PMCDD/Fs; M = methyl), polyhalogenated biphenyls (PXBs, X = Br, Cl), polybrominated diphenyl ethers (PBDEs), pentabromophenols (PBPs), and tetrabromobisphenol-A (TBBP-A). We also evaluate congener-specific relative potencies (REPs) and efficacies (% of TCDDmax) and discuss the dose-response curves of these compounds, as well as the dioxin-like potency of several other Ah-receptor agonists, such as those of the polyaromatic hydrocarbons (PAHs) and polychlorinated naphthalenes (PCNs). The highest REP values were found for several PXDD/F congeners, followed by some coplanar PXBs, trichlorinated PCDD/Fs, PAHs, PBDE-126, 1-6-HxCN, and some brominated flame retardants (TBBP-A). These in vitro investigations indicate that further research is necessary to evaluate more Ah-receptor agonists for dioxin-like potency. (C) 2003 Elsevier Ltd. All rights reserved.