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体外评估 2,2',4,4'-四溴二苯醚(BDE47)和相关羟基化类似物(HO-PBDEs)的内分泌干扰活性。

In vitro profiling of endocrine disrupting potency of 2,2',4,4'-tetrabromodiphenyl ether (BDE47) and related hydroxylated analogs (HO-PBDEs).

机构信息

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China.

出版信息

Mar Pollut Bull. 2011;63(5-12):287-96. doi: 10.1016/j.marpolbul.2011.04.019. Epub 2011 Jul 6.

Abstract

The potential of 2,2',4,4'-tetrabromodiphenyl ether (BDE47) and its related hydroxylated analogs (2'-HO-BDE28, 6-HO-BDE47, 4'-HO-BDE17, and 4'-HO-BDE49) to modulate estrogen/thyroid/androgen receptor-(ER, TR, AR), mediated responses were investigated by use of reporter gene assays. Exposure to 1 or 10 μM, 4'-HO-BDE17 significantly up-regulated expression of Luc, whereas other four chemicals did not induce Luc expression under control of the ER. Anti-estrogenic potency was observed for 4'-HO-BDE17 (IC50=1.14 μM)>6-HO-BDE47 (IC50=2.65 μM)>2'-HO-BDE28 (IC50=9.49 μM)>BDE47 (IC50=21.11 μM). No anti-estrogenic effect of 4'-HO-BDE49 was observed. Both 4'-HO-BDE17, 4'-HO-BDE49 resulted in greater responses of Luc expression induced by T3. BDE47, 2'-HO-BDE28, 6-HO-BDE47 did not show any effect on the expression of Luc induced by 5 nM T3. 6-HO-BDE47 (IC50=0.34 μM)>4'-HO-BDE17 (IC50=1.41 μM)>BDE47 (IC50=3.83 μM)>2'-HO-BDE28 (IC50=29.22 μM) exhibited anti-androgenic potency, while 4'-HO-BDE49 did not show androgenic transcriptional activity.

摘要

四溴二苯醚(BDE47)及其相关的羟基类似物(2'-HO-BDE28、6-HO-BDE47、4'-HO-BDE17 和 4'-HO-BDE49)具有调节雌激素/甲状腺激素/雄激素受体(ER、TR、AR)介导的反应的潜力,本研究利用报告基因检测法对此进行了研究。暴露于 1 或 10 μM 的 4'-HO-BDE17 可显著上调 Luc 的表达,而其他四种化学物质在 ER 控制下不会诱导 Luc 表达。4'-HO-BDE17(IC50=1.14 μM)>6-HO-BDE47(IC50=2.65 μM)>2'-HO-BDE28(IC50=9.49 μM)>BDE47(IC50=21.11 μM)具有抗雌激素作用。4'-HO-BDE49 没有表现出抗雌激素作用。4'-HO-BDE17 和 4'-HO-BDE49 均导致 T3 诱导的 Luc 表达产生更大的反应。BDE47、2'-HO-BDE28 和 6-HO-BDE47 对 5 nM T3 诱导的 Luc 表达没有任何影响。6-HO-BDE47(IC50=0.34 μM)>4'-HO-BDE17(IC50=1.41 μM)>BDE47(IC50=3.83 μM)>2'-HO-BDE28(IC50=29.22 μM)表现出抗雄激素作用,而 4'-HO-BDE49 没有表现出雄激素转录活性。

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