Environmental Disruptors of Reproductive Physiology

生殖生理的环境干扰因素

• 批准号: 6524871
• 负责人: Kathleen Frances Arcaro
• 金额: $ 9.28万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524871
• 关键词: MCF7 cell; carbopolycyclic compound; chemical carcinogenesis; environmental exposure; environmental toxicology; estrogen inhibitor; estrogen receptors; gene environment interaction; gene expression; halobiphenyl /halotriphenyl compound; hormone regulation /control mechanism; laboratory rat; mammary gland; microarray technology; northern blottings; polymerase chain reaction; radiofluorescent probe; receptor binding; reproductive development; thin layer chromatography; tissue /cell culture; toxicant interaction; toxin metabolism

OVERALL DESCRIPTION (provided by applicant) The purpose of this proposal is to provide Dr. Arcaro with release-time from teaching and administration so that she can devote 100% of her professional efforts to developing her research career by incorporating modem molecular genetic techniques into her research program. Dr. Arcaro is a Research Assistant Professor in the Department of Environmental Health and Toxicology, School of Public Health, University at Albany. Her newly established laboratory, is on the East Campus, a center for the University, at Albany's new initiative to promote research in science and technology. Dr. Arcaro s immediate research goal is to determine the mechanisms by which mixtures of polychlorinated biplienyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) disrupt estrogenic responses. Her long-term career objectives are to understand how exposure to toxic environmental chemicals impacts human health, and contribute knowledge that will ultimately lesson the burden of environmentally-related diseases. There is widespread concern that exposure to chemicals in the environment may, be related to the observed increase in the incidence of breast cancer. PCBs and PAHs are of particular concern due to their potential to disrupt estrogenic responses. It is difficult to predict the health effects of exposure to complex mixtures of these chemicals because individual congeners of PCBs and PAHs can be either estrogenic or antiestrogenic and act through a variety of mechanisms potentially leading to additive. Antagonistic or synergistic effects. Furthermore, the microbial reductive dechlorination of PCBs and the metabolic transformation of both PCBs and PAHs within the body may substantially alter the activity of these mixtures. It is hypothesized that reductive dechlorination of PCBs increases the estrogenic activity of the resulting mixture, and that metabolism of PCBs and PAHs further alters the estrogenic and antiestrogenic activity of these mixtures. Thus, the objective of the research project is to determine how mixtures of PCBs and PAHs may interact and modulate estrogenic activity, in humans. Dr. Arcaro's career development plan includes learning to use modern molecular genetic techniques to determine the ways in which exposure to environmental toxicants affects human health. Specifically, she will: 1) test the will hypothesis that the estrogen receptor plays a role in the carcinogenicity of PAHs, and 2) examine the modulation of gene expression (using microarray technology) in breast cells exposed to complex mixtures of environmental toxicants.

总体描述（由申请人提供） 该提案的目的是向Arcaro博士提供从 教学和管理，以便她可以专业人数100％ 通过合并调制解调器分子来发展她的研究生涯 遗传技术进入她的研究计划。 Arcaro博士是一项研究 环境健康与毒理学系助理教授， 奥尔巴尼大学公共卫生学院。 她的新成立 实验室位于东部校园，大学的中心，位于奥尔巴尼的 旨在促进科学技术研究的新计划。 Arcaro博士 直接研究目标是确定混合物的机制 多氯联苯（PCB）和多环芳烃（PAHS） 破坏雌激素反应。 她的长期职业目标是 了解暴露于有毒环境化学物质如何影响人类健康， 并有助于最终向负担的知识 与环境有关的疾病。 人们普遍担心暴露 对于环境中的化学物质，可能与观察到的增加有关 乳腺癌的发生率。 PCB和PAH特别关注 它们可能破坏雌激素反应。 很难 预测暴露于这些化学物质复杂混合物的健康影响 因为PCB和PAH的个别同类物可以是雌激素的或 抗雌激素和通过各种可能导致的机制作用 添加剂。 对抗或协同作用。 此外，微生物 PCB的还原脱氯和两个PCB的代谢转化 体内的PAH可能会大大改变这些活性 混合物。 假设PCB的还原性脱氯增加 所得混合物的雌激素活性和PCB的代谢 PAHS进一步改变了这些的雌激素和抗雌激素活性 混合物。 因此，研究项目的目的是确定 PCB和PAH的混合物可能相互作用并调节雌激素活性，在 人类。 阿卡罗博士的职业发展计划包括学习使用现代 分子遗传技术，以确定暴露于 环境有毒物质会影响人类健康。 特别是她将：1）测试 遗嘱假说，即雌激素受体在 PAH的致癌性，2）检查基因表达的调节 （使用微阵列技术）在暴露于复杂混合物的乳房中 环境有毒物质。