NOVEL BIOASSAY/BIOMARKER SYSTEMS TO DETECT ESTROGEN AGONISTS IN COMPLEX MIXTURES

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Reproduction and development are highly integrated, hormonally dependent processes that can be acutely sensitive to chemical insult. Several halogenated polycyclic aromatic hydrocarbons, which are common Superfund contaminants, exhibit agonist as well as antagonist hormonal activity and are therefore potential reproductive and developmental toxicants. This project is composed of three subprojects. Each subproject has a different approach to the study of reproductive toxicity, yet the subprojects share the overall objectives of (1) characterizing the effects of selected halogenated polycyclic aromatic hydrocarbons on reproduction and development, (2) investigating the mechanisms that initiate and mediate the chemical-induced alterations in reproduction and development, (3) assessing possible health risks arising from exposure to these chemicals. This subproject will study chemical estrogenicity by developing in vitro bioassay systems of human, rodent and fish cell lines stably transfected with an estrogen-responsive genetically engineered luciferase reporter system. The response of transfected cell lines will be compared to other measures of estrogenicity such as the mouse in vivo uterotropic assay and MCF-7 cell line proliferation. These bioassay systems will enable rapid assessment of estrogenicity of complex environmental mixtures.