In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol A compounds.
In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol A compounds.
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多溴二苯基醚，羟基化的PDBE和多溴化的双酚A化合物的体外雌激素。
DOI：
10.1289/ehp.01109399
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发表时间：
2001-04
影响因子：
10.4
通讯作者：
Brouwer, A
中科院分区：
文献类型：
--
作者：
Meerts, IATM;Letcher, RJ;Hoving, S;Marsh, G;Bergman, Å;Lemmen, JG;van der Burg, B;Brouwer, A
多溴联苯醚(PBDEs)在塑料和纺织材料中被大量用作添加剂阻燃剂。多溴二苯醚是一种持久性化合物，已在野生动物、人类脂肪组织和血浆样本中检测到。在这项研究中，我们基于雌激素受体(ER)依赖的荧光素酶报告基因的表达，在三种不同的细胞系中研究了几种PBDE同系物、三种羟基化的PBDEs(HO-PBDEs)和不同溴化的双酚A化合物的(抗)雌激素活性。在稳定转染雌激素反应荧光素酶报告基因(pEREtata-Luc)的人T47D乳腺癌细胞中，11种多溴二苯醚显示出雌激素活性，其浓度导致50%诱导(EC(50))从2.5微米到7.3微米不等。最强的HO-PBDE[2-溴-4-(2，4，6-三溴苯氧基)苯酚]对荧光素酶的诱导作用超过雌二醇(E(2))，尽管浓度高出50,000倍。正如预期的那样，溴化度最低的溴化双酚A化合物具有最高的雌激素活性(3-单溴双酚A的EC(50)值为0.5微米)。在ERα特异、稳定转染人胚胎肾细胞系(293-ERα-Luc)中，HO-PBDE 4-(2，4，6-三溴苯氧基)苯酚是一种高效雌激素，EC(50)<；0.1微米，最大诱导倍数为35-40倍，与E(2)相似。在类似的ERβ特异的293-ER Betas-Luc细胞系中，4-(2，4，6-三溴苯氧基)苯酚的激动力要低得多(与E(2)相比最大诱导50%)，但EC(50)值相当。这些结果表明，几种纯的PBDE同系物，特别是HO-PBDEs和溴化双酚A类似物，既是ERα受体的激动剂，也是ERβ受体的激动剂，从而在体外刺激ER介导的荧光素酶的诱导。这些数据还表明，多溴二苯醚在体内的代谢可能会产生更有效的假雌激素。
Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.
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DOI：
10.1007/bf00325850
发表时间：
1993-06-01
期刊：
FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY
影响因子：
--
作者：
BALLSCHMITER, K;MENNEL, A;BUYTEN, J
通讯作者：
BUYTEN, J
DOI：
10.1073/pnas.93.22.12581
发表时间：
1996-10-29
影响因子：
11.1
作者：
Dellovade, TL;Zhu, YS;Pfaff, DW
通讯作者：
Pfaff, DW
影响因子：
4.5
作者：
FOWLES, JR;FAIRBROTHER, A;KERKVLIET, NI
通讯作者：
KERKVLIET, NI
影响因子：
4.8
作者：
Kuiper, GGJM;Lemmen, JG;Gustafsson, JÄ
通讯作者：
Gustafsson, JÄ
影响因子：
4.8
作者：
Kuil, CW;Brouwer, A;van der Burg, B
通讯作者：
van der Burg, B