BIOSENSOR STUDIES OF ESTROGENIC COMPOUNDS WITH HER-A & B

1999年，环境保护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一样结合hER。 需要一种方法来区分两者。 IA，Inc.提出了一个广泛的和独特的应用，其光纤传感器检测雌激素模拟物，以测试一个创新的方法来解决这个问题的可行性。 拟议的工作将测试的假设，这种区别是有关的可测量的动力学差异，其中hER-α和hER-β结合和解离的雌激素反应元件。 根据该提案的具体目标，James Wittliff博士将建立，荧光标记和表征hER-β的供应。 IA Inc.将创建具有雌激素配体或雌激素反应元件的纤维传感器。将使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之间结合动力学的影响。 将研究10-10-10- 5 M之间的浓度，并将其与高剂量和低剂量许多雌激素化合物的生物效应差异的文献报告相关联。建议的商业应用化学工业和EPA测试实验室需要相对低成本（10，000美元）的便携式仪器，其具有用于测试环境中化学品的雌激素活性的试剂。 这项研究将提供界定该文书适用范围的数据。

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.