BIOSENSOR STUDIES OF ESTROGENIC COMPOUNDS WITH HER-A & B

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In 1999 the EPA will begin Tier 1 screening of chemicals for endocrine disrupting potential. Screening includes assessment of interactions with estrogen receptor (hER). Beneficial phytoestrogens bind hER as do harmful synthetic estrogens. A method is needed which distinguishes one from the other. IA, Inc. proposes an extensive and unique application of its fiber optic sensor for detecting estrogen mimics so as to test the feasibility of an innovative approach to this problem. The proposed work will test the hypothesis that this distinction is related to measurable differences in the kinetics with which hER- alpha and hER-beta bind to and dissociate from the estrogen response element. Under the specific aims of this proposal Dr. James Wittliff will establish, fluorophore-label and characterize a supply of hER-beta. IA Inc. will create fiber sensors possessing either estrogenic ligand or estrogen response element. The effects of phytoestrogens, xenoestrogens, and endogenous estrogens on the kinetics of binding between estrogen response element and hER-alpha and beta will be studied using the fiber optic sensor. Concentrations between 10-10-10-5M will be studied and related to literature reports of differences in the biological effects of high and low doses of many estrogenic compounds. PROPOSED COMMERCIAL APPLICATION A relatively low cost (10,000 dollars) portable instrument with reagents for testing chemicals in the environment for estrogenic activity is needed by the chemical industry and by EPA testing laboratories. This research will provide data which defines the scope of application of the instrument.