Biomarkers and mechanisms of metal and mixed metal exposures

金属和混合金属暴露的生物标志物和机制

• 批准号: 10353202
• 负责人: LAURIE G HUDSON
• 金额: $ 35.08万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10353202
• 关键词: Acute; Address; Adult; Adverse effects; Antioxidants; Arsenic; Atherosclerosis; Autoimmunity; Biological; Biological Markers; Biological Monitoring; Blood Vessels; Cell model; Cells; Chronic; Chronic Disease; Clinical Trials; Collection; Communities; Community Health; DNA Damage; DNA Repair Gene; DNA Repair Inhibition; Data; Decision Making; Detection; Development; Diabetes Mellitus; Disease; Environment; Environmental Exposure; Environmental Health; Environmental Protection; Evaluation; Experimental Models; Exposure to; Future; Generations; Goals; Health; Health Priorities; Health Surveys; Human; Hypertension; Immune; Immune Targeting; Immunologics; Individual; Inflammation; Inflammatory; Inflammatory Response; Intervention; Kidney Diseases; Knowledge; Link; Lung; Metal exposure; Metals; Micronutrients; Mining; Modification; Native Americans; New Mexico; Nutrient; Nutrition Surveys; Outcome; Oxidation-Reduction; Oxidative Stress; Oxidative Stress Induction; Pattern; Population; Population Study; Process; Production; Proteins; Publishing; Reactive Oxygen Species; Research; Risk; Risk Assessment; Risk Reduction; Sampling; Science; Selenium; Signal Recognition Particle; Signal Transduction; Site; Superfund; Testing; Time; Toxic effect; Universities; Uranium; Vanadium; Work; Zinc; Zinc Fingers; base; biological adaptation to stress; cytokine; cytotoxicity; dietary; experimental study; exposure pathway; exposure route; immunoregulation; immunotoxicity; insight; macromolecule; member; metal poisoning; model design; population based; programs; therapy development; toxic metal; tribal lands; uptake; wasting

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.

项目＃1 - 社区暴露（BP COMM）的生物投影 - 摘要 与合作的美国原住民社区，对金属金属的暴露和毒性评估 西南部（UNM金属）团队的部落土地已获得社区层面暴露的证据 以及与部落上1100多个废弃铀矿（AUM）废物相关的健康风险 土地。生物监测结果证实，社区成员暴露于铀和其他金属 除了国家规范之外，还引起了人们对健康影响的担忧。根据已发布和 初步发现，我们将检验以下假设，即暴露于环境金属的独特混合物 与AUM相关的促进氧化应激和炎症反应，已知可以促进的过程 免疫失调和多种慢性疾病的发展。此外，我们假设 可以根据特定金属和金属的毒性机制来阐明饮食缓解策略 混合物。在AIM 1中，我们将努力描述通过生物监测检测到的金属之间的关联和 氧化应激，感染和免疫调节的生物标志物。 AIM 1的发现有望 提供有关环境金属暴露的系统性后果的关键信息。虽然铀 一直是社区关注的重点，UNM金属环境项目的发现以及 人类的生物监测强调，其他有毒金属在环境中很普遍，并且存在于 人口的水平。 AIM 2中的实验研究将集中于社区产生的氧化应激 - 相关金属和金属混合物作为一种基本机制，导致炎症发生改变 反应和免疫调节。我们将选择在 社区优化AIM 2研究的人类相关性。将进行详细的机械分析 建立金属相互作用的基础，包括潜在的有益金属金属相互作用 抗氧化金属微量营养素（锌/Zn和硒/SE）。锌和SE与有毒的相互作用的研究 金属和金属混合物可能会为缓解环境的不利影响提供可访问的策略 人口中的金属暴露。该项目对社区的关注和成果有反应 预计1）提供对在 环境样本并提高了社区的生物测量，2）扩大机械知识 特定金属和金属混合物的影响以及金属的基础：人类的金属相互作用 免疫细胞和3）实验测试基于机制的干预措施提供保护的潜力 来自环境金属的暴露。 BP COMM解决SRP命令1、2和4：检测和 分别评估效果，风险评估和降低风险。