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: 6217622
• 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/6217622
• 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.

生殖和发育是高度结合的， 对化学污染非常敏感的过程。 几 卤化多环芳烃，这是常见的超级基金 污染物，表现出激动剂以及拮抗剂激素活性， 因此是潜在的生殖和发育毒物。 这 该项目由三个分项目组成。 每个子项目都有一个 研究生殖毒性的不同方法，但 分项目的总体目标是：（1）确定 选定的卤化多环芳烃对 生殖和发育，（2）调查机制， 启动和介导化学诱导的生殖改变， （3）评估暴露可能引起的健康风险 这些化学品。 这个子项目将研究化学雌激素 通过开发人类、啮齿动物和鱼类细胞的体外生物测定系统， 稳定转染雌激素反应性基因的细胞系 工程化荧光素酶报告系统。 转染细胞的反应 线将比较其他措施的雌激素，如 小鼠体内子宫促分化试验和MCF-7细胞系增殖。 这些 生物测定系统将能够快速评估复合物的雌激素活性 环境混合物。