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PARENT SESSION

PT03 Persistent Organic Pollutants (POPs)
Exhibit Hall
8:00 AM - Tuesday

(PT031) Chronic exposure to TCDD increases estradiol-sensitivity and decreases antiestrogen-sensitivity in MCF-7 cells.

Marquez-Bravo, L.1, Gierthy, J.1, 2, 1 State University of New York at Albany, School of Public Health, Albany, NY, USA2 Wadsworth Center, New York State Department of Health, Albany, NY, USA

ABSTRACT- Background and significance: 2,3,7,8-Tetrachrolodibenzo-p-dioxin (TCDD) is a ubiquitous, persistent, organic pollutant. TCDD has been classified as an anti-estrogen because it interferes with the estrogenic response in various biological systems. However, acquired resistance to the anti-estrogenic effects of TCDD has been observed in in vivo models. Recent epidemiological studies suggest that TCDD may be involved in an increased risk of breast cancer. Because of the long half-life of TCDD, it is hypothesized that its effects on breast cancer, if any, might only be evident after a long-term exposure to the compound. Method: MCF-7 human breast cancer cells were cultured for one year in 1 nM of TCDD. These cells (LTDX) were tested in the MCF-7 Focus Assay for their response to 17-beta-estradiol (E2) compared with non-exposed MCF-7 cells. The Focus Assay relies on the ability of the MCF-7 cells to develop dose-dependent three-dimensional multi-cellular nodules or foci in the presence of E2 as well as other estrogens. TCDD and the anti-estrogen ICI 182780 (ICI) inhibit the formation of these foci. Results: LTDX cells are more responsive to the foci stimulatory effects of E2 and more resistant to the anti-estrogenic effects of ICI, as compared to control MCF-7 cells. Moreover, in LTDX cells, an additive effect between TCDD and E2 was observed. Conclusion: breast epithelial cells exposed for prolonged periods to TCDD respond with increased sensitivity to the foci stimulatory effects of E2 and are more resistant to anti-estrogens and these effects may be altered by the chronic presence of E2.

Key words: MCF-7, TCDD, breast cancer, chronic exposure


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