Environmental estrogen stimulation of growth and estrogen receptor function in preneoplastic and cancerous human breast cell lines.
BACKGROUND
DDT and polychlorinated biphenyls (PCBs), which are widespread in the ecosystem, can mimic estrogen-mediated 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< or =.001), whereas Aroclor 1221 and Aroclor 1254, both individually and in combination, are only weakly estrogenic.


CONCLUSIONS
p,p'-DDT is the most effective organochlorine in regulating estrogen receptor-mediated 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.
Shekhar
P V
PV
Karmanos Cancer Institute, and Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA. shekharm@kci.wayne.edu
Werdell
J
J
Basrur
V S
VS
D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D002273:Carcinogens / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D003634:DDT / Q000009:adverse effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D011960:Receptors, Estrogen / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D011960:Receptors, Estrogen; D003634:DDT; D011078:Polychlorinated Biphenyls