Biomarkers and mechanisms of metal and mixed metal exposures

项目#1 -社区暴露生物项目（BP Comm）-摘要 与美国原住民社区合作，UNM金属接触和毒性评估 西南部落土地（UNM金属）团队已经获得了社区水平暴露的证据 和健康风险与1100多个废弃的铀矿（AUM）废物场在他们的部落 之地生物监测结果证实，社区成员暴露于铀和其他金属 超出了国家规范，导致对健康潜在影响的担忧。根据出版的和 初步研究结果，我们将测试的假设，暴露于独特的混合物的环境金属 与AUM相关的促进氧化应激和炎症反应的过程，已知促进 免疫失调和许多慢性疾病的发展。此外，我们假设， 饮食缓解策略可以根据特定金属和金属的毒性机制来阐明， 混合物。在目标1中，我们将努力描绘生物监测检测到的金属之间的关联， 氧化应激、炎症和免疫调节的生物标志物。目标1的研究结果预计将 提供关于环境金属暴露的系统性后果的重要信息。虽然铀 一直是社区关注的焦点，UNM METALS环境项目的调查结果， 人类生物监测突出表明，其他有毒金属在环境中普遍存在， 人口水平。目标2中的实验研究将集中在社区产生的氧化应激， 相关金属和金属混合物作为导致炎症改变的潜在机制， 反应和免疫调节。我们将选择实验终点和观察到的暴露模式， 社区优化目标2研究的人类相关性。将进行详细的机理分析 建立金属相互作用的基础，包括潜在的有益的金属-金属相互作用， 抗氧化金属微量营养素（锌/锌和硒/硒）。锌、硒与毒物相互作用的研究 金属和金属混合物可以为减轻环境污染的不利影响提供信息 人类的金属接触。该项目是回应社区的关注和成果， 预计将1）深入了解中发现的未充分研究的有毒金属的生物后果 环境样品和生物标本中的升高，2）扩大机械知识 特定金属和金属混合物的影响以及金属与金属在人体内相互作用的基础 免疫细胞，以及3）实验测试基于机制的干预措施的潜力，以提供保护 环境金属暴露。BP通信解决SRP任务1、2和4：检测和 效果评价、风险评估和风险降低。

Project #1 – BioProject on Community Exposures (BP Comm) - SUMMARY With partnering Native American communities, the UNM Metals Exposure and Toxicity Assessment on Tribal Lands in the Southwest (UNM METALS) team has obtained evidence for community level exposures and health risks associated with more than 1100 abandoned uranium mine (AUM) waste sites on their tribal lands. Biomonitoring results confirm that community members are exposed to uranium and other metals beyond national norms, leading to concerns about potential impact on health. Based on published and preliminary findings, we will test the hypothesis that exposure to the unique mixtures of environmental metals associated with AUMs promotes oxidative stress and inflammatory response, processes known to promote immune dysregulation and development of numerous chronic diseases. Furthermore, we hypothesize that dietary mitigation strategies can be elucidated based on mechanisms of toxicity of specific metals and metal mixtures. In Aim 1 we will work to delineate associations between metals detected by biomonitoring, and biomarkers of oxidative stress, inflammation and immune modulation. The findings from Aim 1 are expected to provide critical information on systemic consequences of environmental metal exposures. Although uranium has been the focus of community concern, findings from the UNM METALS Environmental Projects and human biomonitoring highlight that other toxic metals are prevalent in the environment and present at elevated levels in the population. Experimental studies in Aim 2 will focus on oxidative stress generated by community- relevant metals and metal mixtures as an underlying mechanism leading to alterations in inflammatory response and immune modulation. We will select experimental endpoints and exposure patterns observed in the community to optimize human relevance of Aim 2 studies. Detailed mechanistic analyses will be performed to establish the basis for metal interactions including potential beneficial metal-metal interactions of the antioxidant metal micronutrients (zinc/Zn and selenium/Se). Studies on Zn and Se interactions with toxic metals and metal mixtures may inform tractable strategies for mitigating the adverse effects of environmental metal exposures in human populations. This project is responsive to community concerns and the outcomes are expected to 1) provide insights into biological consequences of understudied toxic metals identified in environmental samples and elevated in biospecimens from the community, 2) expand mechanistic knowledge of the impact of specific metals and metal mixtures as well as the basis for metal:metal interactions in human immune cells, and 3) experimentally test the potential of mechanism-based interventions to confer protection from environmental metal exposures. BP Comm addresses SRP mandates 1, 2 and 4: Detection and Evaluation of Effects, Risk Assessment and Risk Reduction, respectively.