Environmental Disruptors of Reproductive Physiology

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OVERALL DESCRIPTION (provided by applicant) The purpose of this proposal is to provide Dr. Arcaro with release-time from teaching and administration so that she can devote 100% of her professional efforts to developing her research career by incorporating modem molecular genetic techniques into her research program. Dr. Arcaro is a Research Assistant Professor in the Department of Environmental Health and Toxicology, School of Public Health, University at Albany. Her newly established laboratory, is on the East Campus, a center for the University, at Albany's new initiative to promote research in science and technology. Dr. Arcaro s immediate research goal is to determine the mechanisms by which mixtures of polychlorinated biplienyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) disrupt estrogenic responses. Her long-term career objectives are to understand how exposure to toxic environmental chemicals impacts human health, and contribute knowledge that will ultimately lesson the burden of environmentally-related diseases. There is widespread concern that exposure to chemicals in the environment may, be related to the observed increase in the incidence of breast cancer. PCBs and PAHs are of particular concern due to their potential to disrupt estrogenic responses. It is difficult to predict the health effects of exposure to complex mixtures of these chemicals because individual congeners of PCBs and PAHs can be either estrogenic or antiestrogenic and act through a variety of mechanisms potentially leading to additive. Antagonistic or synergistic effects. Furthermore, the microbial reductive dechlorination of PCBs and the metabolic transformation of both PCBs and PAHs within the body may substantially alter the activity of these mixtures. It is hypothesized that reductive dechlorination of PCBs increases the estrogenic activity of the resulting mixture, and that metabolism of PCBs and PAHs further alters the estrogenic and antiestrogenic activity of these mixtures. Thus, the objective of the research project is to determine how mixtures of PCBs and PAHs may interact and modulate estrogenic activity, in humans. Dr. Arcaro's career development plan includes learning to use modern molecular genetic techniques to determine the ways in which exposure to environmental toxicants affects human health. Specifically, she will: 1) test the will hypothesis that the estrogen receptor plays a role in the carcinogenicity of PAHs, and 2) examine the modulation of gene expression (using microarray technology) in breast cells exposed to complex mixtures of environmental toxicants.