POLYCHLORINATED-BIPHENYLS (PCBS), DIBENZO-P-DIOXINS (PCDDS), AND DIBENZOFURANS (PCDFS) AS ANTIESTROGENS IN MCF-7 HUMAN BREAST-CANCER CELLS - QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS

被引:154
作者
KRISHNAN, V
SAFE, S
机构
[1] TEXAS A&M UNIV SYST,DEPT VET PHYSIOL & PHARMACOL,COLL STN,TX 77843
[2] TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLL STN,TX 77843
关键词
D O I
10.1006/taap.1993.1086
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 (10-6 Ni). 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. © 1993 Academic Press. All rights reserved.
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页码:55 / 61
页数:7
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