Mentored Training in Research on Arsenic

描述(由申请人提供) 此应用程序的目标是支持应聘者在 以病人为中心的研究。这将通过一个计划结合在一起来完成 讲授、指导和科学研究的重点是 摄入砷的药代动力学研究。全世界数以百万计的人 暴露在饮用水中的砷，最近的证据表明 这些暴露可能会导致患肺癌的巨大风险。目前， 对其人体毒代动力学或肺部毒性知之甚少。 摄入了砷。候选人提出了三项关于暴露在砷中的研究 增加我们对这些主题的了解。第一个将评估 13种饮食和代谢因素在砷甲基化中的作用 无机砷的主要解毒途径。血清中这些物质的水平 这些因素将与基于尿液的砷甲基化模式进行比较 排出砷的代谢物。此前的研究表明， 个体对砷的甲基化程度差异很大，因此 研究调节甲基化的因素可能会使易感亚甲基化 将被识别的人口，因此可以提供有用的信息 饮用水监管。第二项研究是一具横断面身体。 砷及其代谢物在细胞内分布的研究 人体组织。这六个器官的组织样本将从20个 在死因验尸官办公室进行例行验尸的受试者 暴露人群和未暴露人群。砷及其代谢物的水平 将在每个器官的亚细胞成分中确定。识别 砷积累的特定模式可能进一步支持这一假说 摄入的砷是一种强烈的肺癌致癌物，这可能解释了为什么 肺似乎比其他组织更容易受到砷的影响。此外, 提供关于特定代谢物分布模式的信息， 尤其是单甲基亚砷酸，可能会增加对 砷致癌过程中的甲基化。最后的项目是设计一个 低暴露饮用水与肺癌的流行病学研究 砷。目前，关于黄曲霉毒素对癌症的影响的信息很少。 砷的剂量低于100微克/升。该项目将涉及开发 研究设计和实施的所有主要方面，最终目标是 准备一项调查，以提供有用的剂量反应数据 饮用水监管。

DESCRIPTION (provide by applicant) The goal of this application is to support the candidate's development in patient-orientated research. This will be done through a program combining didactic teaching, mentoring, and scientific research focusing on the pharmacokinetics of ingested arsenic. Millions of people worldwide are exposed to arsenic in their drinking water, and recent evidence suggests that these exposures may lead to substantial risks of lung cancer. Currently, little is known about the human toxicokinetics or pulmonary toxicity of ingested arsenic. The candidate proposes three studies in arsenic exposed populations to increase our knowledge of these topics. The first will assess the role of 13 dietary and metabolic factors in arsenic methylation, the primary detoxification pathway of inorganic arsenic. Serum levels of these factors will be compared to arsenic methylation patterns based on the urinary excretion of arsenic metabolites. Previous studies have shown that individuals vary greatly in the degree they methylate arsenic, thus investigating factors that regulate methylation may allow susceptible sub- populations to be identified, and therefore may provide information useful in drinking water regulation. The second study is a cross-sectional cadaver study on the intracellular distribution of arsenic and its metabolites in human tissues. Tissue samples from the six organs will be collected from 20 subjects during routine autopsies performed by the coroners offices of arsenic exposed and unexposed population. The levels of arsenic and its metabolites will be determined in the subcellular components of each organ. Identifying specific patterns of arsenic accumulation may further support the hypothesis that ingested arsenic is a potent lung carcinogen, and may explain why the lung appears more susceptible to arsenic than other tissues. In addition, providing information on the distribution patterns of specific metabolites, particularly monomethylarsonous acid, may add new insight into the role of methylation in arsenic carcinogenesis. The final project is the design of an epidemiological study of lung cancer and low exposures of drinking water arsenic. Currently, little information is available on the cancer effects of arsenic at doses below 100 ug/L. This project will involve the development of all major aspects of study design and implementation with the ultimate goal of preparing an investigation that will provide dose-response data useful in drinking water regulation.