Project 3: Arsenic Biomarker Epidemiology

项目3：砷生物标志物流行病学

• 批准号: 7089425
• 负责人: ALLAN H SMITH
• 金额: $ 39.37万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7089425
• 关键词: Africa; South America; arsenic; biomarker; clinical research; clinical trials; early experience; environmental exposure; environmental toxicology; epidemiology; genetic polymorphism; lung neoplasms; metabolism; proteomics; urinalysis; Africa; South America; arsenic; biomarker; clinical research; clinical trials; early experience; environmental exposure; environmental toxicology; epidemiology; genetic polymorphism; lung neoplasms; metabolism; proteomics; urinalysis

Millions of people are exposed to arsenic-contaminated water in the U.S. and worldwide, and arsenic is ranked first on the most recent priority list of Superfund site hazardous substances. Current evidence suggests that lung cancer is the leading cause of arsenic-associated mortality. In addition, arsenic also increases the incidence of non-malignant pulmonary disease, and intriguing preliminary evidence obtained by our research group suggests that those exposed as young children or in utero are particularly susceptible to both the malignant and non-malignant pulmonary effects of arsenic. We propose a series of investigations to further explore the effects of childhood arsenic exposure and the mechanisms that may confer susceptibility to these effects. The proposed epidemiological studies include a case-control study of childhood and in utero arsenic exposure and subsequent risks of lung cancer in young adults in Northern Chile, and a cross-sectional study of lung function and respiratory health and arsenic exposure involving children in West Bengal. In addition, biological samples collected during these studies, combined with samples collected from several of our past studies, will be used for additional investigations on arsenic susceptibility and mechanisms of toxicity including: 1). Susceptibility related to individual differences in urinary concentrations of MMA3, a highly toxic but rarely studied arsenic metabolite; 2). Susceptibility related to genetic polymorphisms, in particular those involving AS3MT (cyt19), GSTO1, GSTM1, and EGFR. 3). Assessment of urinary proteomic patterns as biomarkers of exposure, disease, and susceptibility. In past years, Superfund has provided the core funding that has allowed us to make many new and important contributions to research on arsenic. Our goal is to continue this successful model, but with a new focus on the respiratory effects of childhood and in utero exposures and the associated mechanisms of toxicity and susceptibility. Given the widespread exposure to ingested arsenic in the U.S. and worldwide, and the very high risks of lung disease following early life exposures we have seen in our preliminary studies, investigating these effects has the potential to yield important new public health and scientific information regarding the in utero and childhood effects of toxic substances.

数以百万计的人在美国和世界范围内暴露于砷污染的水中，砷是 在超级基金场地危险物质的最新优先级清单中排名第一。当前的证据 表明肺癌是砷相关死亡率的主要原因。另外，砷也 增加非恶性肺疾病的发生率以及获得的有趣的初步证据 由我们的研究小组提出，尤其是在年幼的孩子或子宫里暴露的人 敏感砷的恶性和非恶性肺作用。我们提出了一系列 调查以进一步探讨儿童砷暴露的影响以及可能的机制 会议对这些影响的敏感性。拟议的流行病学研究包括一项案例对照研究 北部年轻人的儿童和子宫砷暴露以及随后的肺癌风险 智利，以及涉及肺功能和呼吸健康和砷暴露的横断面研究 西孟加拉邦的孩子。此外，在这些研究期间收集的生物样品以及 从我们过去的几项研究中收集的样本将用于砷的其他研究 毒性的敏感性和机制，包括：1）。与个体差异有关的易感性 MMA3的尿液浓度是一种剧毒但很少研究的砷代谢产物； 2）。敏感性 与遗传多态性有关，尤其是涉及AS3MT（CYT19），GSTO1，GSTM1和 egfr。 3）。评估尿蛋白质组学模式作为暴露，疾病和 敏感性。在过去的几年中，超级基金提供了核心资金，使我们能够制造许多 对砷研究的新重要贡献。我们的目标是继续这个成功的模型，但是 新的重点是儿童期和子宫暴露的呼吸作用以及相关的 毒性和敏感性的机制。鉴于美国广泛暴露于摄入的砷 和全世界，以及我们在早期生命暴露后出现的肺部疾病的高风险 初步研究，调查这些影响有可能产生重要的新公共卫生和 有关有毒物质的子宫内和儿童期影响的科学信息。