Environmental Disruptors of Reproductive Physiology

整体描述(由申请人提供) 这项提议的目的是为Arcaro博士提供从 教学和行政，这样她就可以100%地投入她的专业 通过融入现代分子来努力发展她的研究事业 将基因技术纳入她的研究计划。阿卡罗博士是一名研究人员 环境卫生与毒理学系助理教授， 奥尔巴尼大学公共卫生学院。她新成立的公司 实验室在东校区，这是奥尔巴尼大学的一个中心 推动科技研究的新举措。阿卡罗·S博士 目前的研究目标是确定混合物的作用机理 多氯联苯和多环芳烃 干扰雌激素反应。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，最终将教会我们 与环境有关的疾病。人们普遍担心，暴露在 对环境中的化学物质的影响，可能与观察到的 乳腺癌的发病率。多氯联苯和多环芳烃尤其值得关注 它们有可能扰乱雌激素反应。很难做到 预测接触这些化学品的复杂混合物对健康的影响 因为多氯联苯和多环芳烃的个别同系物可能是雌激素或 抗雌激素，并通过多种机制发挥作用，可能导致 添加剂。拮抗或协同作用。此外，微生物 多氯联苯的还原脱氯及其代谢转化 体内的多环芳烃可能会显著改变这些物质的活性 混合物。假设多氯联苯的还原脱氯增加 产生的混合物的雌激素活性以及多氯联苯的代谢 而多环芳烃进一步改变了这些化合物的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能相互作用并调节雌激素活性，在 人类。Arcaro博士的职业发展计划包括学习使用现代 分子遗传学技术，以确定暴露于 环境毒物影响人类健康。具体地说，她将：1)测试 关于雌激素受体在高血压中起作用的意志假设 多环芳烃的致癌性，以及2)检测基因表达的调节 (使用微阵列技术)暴露于复杂的 环境毒物。

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.