POLYCHLORINATED-BIPHENYLS (PCBS), DIBENZO-P-DIOXINS (PCDDS), AND DIBENZOFURANS (PCDFS) AS ANTIESTROGENS IN MCF-7 HUMAN BREAST-CANCER CELLS - QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS
POLYCHLORINATED-BIPHENYLS (PCBS), DIBENZO-P-DIOXINS (PCDDS), AND DIBENZOFURANS (PCDFS) AS ANTIESTROGENS IN MCF-7 HUMAN BREAST-CANCER CELLS - QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS
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DOI：
10.1006/taap.1993.1086
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发表时间：
1993-05-01
影响因子：
3.8
通讯作者：
SAFE, S
中科院分区：
文献类型：
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作者：
KRISHNAN, V;SAFE, S
在芳基烃 (Ah) 反应性 MCF-7 人乳腺癌细胞系中测定了几种 PCB、PCDD 和 PCDF 同系物以及几种商业 PCB 制剂作为抗雌激素的浓度依赖性效应。使用聚丙烯酰胺凝胶电泳、用 155 ProBlue 和银染对蛋白质条带进行双重染色以及通过光密度分析进行定量，测量对 17β-雌二醇诱导的 52 kDa 蛋白质（组织蛋白酶 D 前体）分泌的抑制。对于多氯联苯，抗雌激素效力的顺序为 3,3',4,4',5-五氯联苯 > 3,3,4,4,5,5'-六氯联苯 3,3',4,4-四氯联苯 > 2,3,3',4,4',5'-六，2,3,3',4,4'- 和 2,3,4,4',5-五氯联苯> Aroclors 1221、1232、1248、1254 和 1260 在本研究中使用的最高浓度 (10−6Ni) 下作为抗雌激素没有活性。对于PCDD和PCDF，抗雌激素效力的顺序为2,3,7,8-四氯二苯并-对二恶英>2,3,7,8-四氯二苯并呋喃>2,3,4,7,8-五氯二苯并呋喃>1,2,3,7,9-五氯二苯并呋喃>1,3,6,8-四氯二苯并呋喃。除了少数例外，所有这些同源物和混合物的效力顺序与它们作为其他 Ah 受体介导的反应的激动剂的相对活性以及它们对 Ah 受体的竞争性结合亲和力平行。这项研究的结果支持了 Ah 受体在介导 MCF-7 细胞中 17β-雌二醇诱导的 52-kDa 蛋白分泌抑制中的作用，并指出了该技术作为此类化合物的生物测定的实用性。
The concentration-dependent effects of several PCB, PCDD, and PCDF congeners and several commercial PCB preparations as antiestrogens were determined in the aryl hydrocarbon (Ah)-responsive MCF-7 human breast cancer cell lines. The inhibition of the 17β-estradiol-induced secretion of the 52-kDa protein (procathepsin D) was measured using a combination of polyacrylamide gel electrophoresis, double-staining of the protein bands with 155 ProBlue and silver stain, and quantitation by densitometric analysis. For the PCBs, the order of antiestrogenic potency was 3,3′,4,4′,5-pentachlorobiphenyl > 3,3,4,4,5,5′-hexachlorobiphenyl 3,3′,4,4-tetrachlorobiphenyl > 2,3,3′,4,4′,5′-hexa, 2,3,3′,4,4′- and 2,3,4,4′,5-pentachlorobiphenyl > Aroclors 1221, 1232. 1248, 1254, and 1260 were inactive as antiestrogens at the highest concentrations used in this study (10−6Ni). For the PCDDs and PCDFs, the order of antiestrogenic potency was 2,3,7,8-tetrachlorodibenzo-p-dioxin > 2,3,7,8-tetrachlorodibenzofuran > 2,3,4,7,8-pentachlorodibenzo-furan > 1,2,3,7,9-pentachlorodibenzofuran > 1,3,6,8-tetrachlo-rodibenzofuran. With few exceptions, the order of potency for all these congeners and mixtures paralleled their relative activities as agonists for other Ah receptor-mediated responses and their competitive binding affinities for the Ah receptor. The results of this study support the role for the Ah receptor in mediating the inhibition of the 17β-estradiol-induced secretion of the 52-kDa protein in MCF-7 cells and also points out the utility of this technique as a bioassay for this class of compounds.