Polynuclear aromatic hydrocarbon carcinogens as antiestrogens in MCF-7 human breast cancer cells: role of the Ah receptor

Chaloupka, K. ; Krishnan, V. ; Safe, S. (1992) Polynuclear aromatic hydrocarbon carcinogens as antiestrogens in MCF-7 human breast cancer cells: role of the Ah receptor Carcinogenesis, 13 (12). pp. 2233-2239. ISSN 0143-3334

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Official URL: http://carcin.oxfordjournals.org/content/13/12/223...

Related URL: http://dx.doi.org/10.1093/carcin/13.12.2233

Abstract

Treatment of MCF-7 cells with 1.0 μM 3-methylcholanthrene (MC) caused a decrease in cell proliferation and [3H]thymidine uptake whereas no effects were observed at a lower (0.1 μM) concentration. Co-treatment of the cells with 1 nM 17β-estradiol plus 0.1 or 1.0 μ MC resulted in a significant inhibition of 17β-estradiol-induced growth and [3H]thymidine uptake. MC also inhibited the 17β-estradiol-induced secretion of the 52 kDa protein (procathepsin D) in MCF-7 cells and caused a concentration-dependent decrease in the nuclear estrogen receptor (ER) as determined by either velocity sedimentation analysis or immunoquantitation with human ER antibodies. The effects of several different polynuclear aromatic hydrocarbon (PAH) congeners on the nuclear ER in MCF-7 cells were also determined. Only those congeners which bound to the aryl hydrocarbon (Ah) receptor, namely benzo[a]pyrene, benz[a]anthracene, 7,12-dimethylbenz[a]anthracene and MC, caused a decrease in nuclear ER levels. In contrast, benzo[ghi]perylene, a congener which did not bind to the Ah receptor did not affect nuclear ER levels in MCF-7 cells. Moreover, with some congeners the decrease in nuclear ER levels could be observed without any significant induction of ethoxyresorufin O-deethylase activity, a P4501A1-dependent monooxygenase. These data suggest that the Ah receptor liganded with MC and related PAHs induced a broad spectrum of antiestrogenic responses in MCF-7 cells and complements the results of previous studies which report the antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other halogenated aromatics which are also Ah receptor agonists.

Item Type:Article
Source:Copyright of this article belongs to Oxford University Press.
ID Code:17319
Deposited On:16 Nov 2010 07:59
Last Modified:17 May 2016 01:58

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