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） 本提案的目的是为Arcaro博士提供从 教学和管理，使她能够投入100%的专业 努力发展她的研究事业，将现代分子 基因技术融入她的研究计划 Arcaro博士是一名研究人员 环境卫生和毒理学系助理教授， 奥尔巴尼大学公共卫生学院。 她新成立的 实验室，是在东校区，一个中心的大学，在奥尔巴尼的 促进科学技术研究的新举措。 阿卡罗博士 目前的研究目标是确定混合物的机制， 多氯联苯（PCBs）和多环芳烃（PAHs） 破坏雌激素反应。 她的长期职业目标是 了解接触有毒环境化学品如何影响人类健康， 并贡献知识，最终将教训的负担， 与环境有关的疾病。 人们普遍担心， 可能与所观察到的 乳腺癌的发病率。 多氯联苯和多环芳烃特别令人关注， 破坏雌激素反应的潜力 很难 预测暴露于这些化学物质的复杂混合物对健康的影响 因为PCBs和PAH的个别同源物可以是雌激素， 抗雌激素，并通过多种机制发挥作用， 添加剂 拮抗或协同作用。 此外，微生物 多氯联苯的还原脱氯和两种多氯联苯的代谢转化 和多环芳烃在体内可能会大大改变这些活性 混合物。 据推测，多氯联苯的还原脱氯作用增加， 所得混合物雌激素活性和多氯联苯的代谢 和多环芳烃进一步改变这些雌激素和抗雌激素活性 混合物。 因此，研究项目的目标是确定如何 多氯联苯和多环芳烃的混合物可以相互作用，调节雌激素活性， 人类 Arcaro博士的职业发展计划包括学习使用现代技术 分子遗传技术来确定暴露于 环境毒物影响人类健康。 具体来说，她将：1）测试 意志假说认为雌激素受体在 多环芳烃的致癌性，以及2）检查基因表达的调节 （使用微阵列技术）暴露于复杂混合物的乳腺细胞 环境毒物