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

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.