© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1774-1782, Copyright © 1997 by Oxford University Press
PV Shekhar, J Werdell and VS Basrur
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. CONCLUSION: 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.
ARTICLES
Environmental estrogen stimulation of growth and estrogen receptor function in preneoplastic and cancerous human breast cell lines
Karmanos Cancer Institute, and Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA. shekharm@kci.wayne.edu
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