BIOSENSOR STUDIES OF ESTROGENIC COMPOUNDS WITH HER-A & B

1999年环保局将开始对可能干扰内分泌的化学品进行一级筛选。筛查包括评估与雌激素受体（hER）的相互作用。有益的植物雌激素与有害的合成雌激素结合hER。需要一种区分两者的方法。IA, Inc.提出将其光纤传感器广泛而独特地应用于检测雌激素模拟物，以测试创新方法解决这一问题的可行性。拟议的工作将验证这样的假设，即这种区别与hER- α和hER- β结合和分离雌激素反应元件的动力学的可测量差异有关。根据本提案的具体目标，詹姆斯·维特利夫博士将建立，荧光团标签和表征her - β供应。IA公司将制造含有雌激素配体或雌激素反应元件的纤维传感器。利用光纤传感器研究植物雌激素、异种雌激素和内源性雌激素对雌激素反应元件与her - α和β结合动力学的影响。将对10-10-10-5米之间的浓度进行研究，并将其与许多雌激素化合物高剂量和低剂量的生物效应差异的文献报告联系起来。化学工业和EPA测试实验室需要一种成本相对较低（10,000美元）的便携式仪器，该仪器带有用于测试环境中化学物质的雌激素活性的试剂。这项研究将提供数据，以确定该仪器的应用范围。

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.