Environmental Estrogen Stimulation of Growth and Estrogen Receptor Function in Preneoplastic and Cancerous Human Breast Cell Lines

Abstract

Background : DDT and polychlorinated biphenyls (PCBs), which are widespread in the ecosystem, can mimic estrogenmediated cell activities. Thus, they can potentially interfere with many physiologic processes. We compared the effects of organochlorines belonging to the DDT and PCB families, alone and in combination, for their ability to influence the estrogen receptor-mediated activities in preneoplastic breast epithelial cells and breast cancer cells. Methods : Multiple assay systems requiring functional estrogen receptor were employed to test estrogen-like activity of organochlorine ligands. Two-sided statistical tests were used to compare the data. Results : p,p '-DDT, the predominant form of DDT in the environment, is a more potent estrogen than o,p '-DDT ( P <.001), although it is less effective than o,p '-DDT in inhibiting the binding of estradiol (natural estrogen) to estrogen receptor. Among the PCBs, Heptachlor is estrogenic (in transient reporter assays; P ⩽.001), whereas Aroclor 1221 and Aroclor 1254, both individually and in combination, are only weakly estrogenic. Conclusion : p,p '-DDT is the most effective organochlorine in regulating estrogen receptormediated cellular responses. In estrogen receptor-positive breast cancer cells, p,p '-DDT evokes responses by itself and enhances the responses in collaboration with estradiol or o,p '-DDT.