F. Gierthy, Ph.D.

[Guest guest]

http://www.albany.edu/tree-tops/docs.sph/superfund/gierthy.html

PCB ESTROGENICITY IN HUMAN BREAST CELLS

F. Gierthy, Ph.D.

Principal Investigator

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This project will test the hypothesis that polychlorinated biphenyls(PCBs)

have estrogenic or antiestrogenic properties that are dependent on both the

structure and metabolism of the specific PCB. Alteration in estrogen

metabolism could provide an additional mechanism for PCB potentiated changes

in neurochemical function. Previous studies have shown that PCBs exhibit

estrogenic effects in non-human systems. Our goal is to evaluate the

estrogenicity of PCBs and their metabolites in human derived systems.

This project is focused on the estrogenic effects of lower chlorinated and

hydroxylated PCBs. Through the use of the MCF-7 Focus Assay it is possible

to assess the estrogenic effects of specific compounds on human breast

cells. MCF-7 breast cells form a uniform cell mosaic, however, foci or

nodules form in those cell cultures affected by estrogenic compounds. This

estrogen dependent growth of cell foci or nodules is inhibited by

antiestrogens, and therefore this assay can be used to quantatively

determine whether a compound is estrogenic or antiestrogenic.

Using the human breast cancer cell line, MCF-7, this project is evaluating

the in vitro estrogenicity and antiestrogenicity of PCB congeners and their

hydroxylated metabolites. To evaluate this, the assay uses the induction of

estrogen dependent end points. These endpoints are increased tissue

plasminogen activity and focal point development (proliferation and

clustering of cells). This allows the development of structure-function

relationships and establishes whether the metabolism of the PCBs in an

essential prerequisite for their estrogenic action.

This project is also characterizing the metabolism in human systems of those

PCB congeners that yield estrogenic metabolites. We are using human P450s in

microsomes from induced or control MCF-7 cells, human hepatocytes and human

P450s expressed in mammalian systems. This demonstrates whether estrogenic

PCB metabolites can be produced by human p450s and will provide a basis for

further determination of whether PCBs play a role in neurotoxicity due to

estrogenic properties. This project is also characterizing the PCB

metabolism potential in microsomes prepared from the liver, brain, kidney,

and uterus of PCB exposed rats generated by the neurotoxicity projects. The

specific congeners used will be those determined to be estrogenic or

antiestrogenic.

Update: September 1996

This project is focused on the characterization of the estrogenic

interaction and the synergistic effects of PCBs. It is also examining how

xenoestrogenic compounds affect natural estrogens.

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We welcome your comments and inquiries. Please forward comments to: Dr.

F. Gierthy, School of Public Health, University at Albany, Wadsworth Center,

Empire State Plaza, PO Box 509, Albany, NY 12201-0509 Gierthy@...

TEL:(518) 474-8195 FAX: (518) 486-1505

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