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

用于检测复杂混合物中雌激素激动剂的新型生物测定/生物标志物系统

• 批准号: 6296559
• 负责人: JOHN P GIESY
• 金额: $ 15.1万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296559
• 关键词: alternatives to animals in research; bioassay; environmental contamination; estrogen analog; estrogen inhibitor; estrogen receptors; halobiphenyl /halotriphenyl compound; method development; receptor binding; recombinant DNA; tissue /cell culture; toxicant screening; transfection

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.

生殖和发育是高度整合的，依赖于激素