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候选人的发展， 病人导向的研究。 这将通过一个程序来完成， 教学，指导和科学研究，重点是 摄入砷的药代动力学。 全世界有数百万人 他们的饮用水中含有砷，最近的证据表明， 这些接触可导致患肺癌的重大风险。 目前， 对人的毒性或肺毒性知之甚少， 摄入砷 候选人提出了三项研究， 让我们的知识更多地了解这些话题。 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。 这些血清水平 因素将比较砷甲基化模式的基础上，尿 砷代谢物的排泄。 以前的研究已经表明 个体在砷的甲基化程度上差异很大， 研究调节甲基化的因素可能会使易感亚甲基化。 人口，因此可以提供有用的信息， 饮用水管理。 第二项研究是一个横断面的尸体 砷及其代谢产物在细胞内分布的研究 人体组织 将从20个器官中收集6个器官的组织样本， 受试者在例行尸检进行的验尸官办公室的砷 暴露和未暴露的人群。 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设 摄入的砷是一种强有力的肺癌致癌物，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，本发明还提供了一种方法， 提供关于特定代谢物的分布模式的信息， 特别是一甲基亚胂酸，可能会增加新的见解的作用， 甲基化在砷致癌中的作用 最后一个项目是设计一个 肺癌与饮水低暴露的流行病学研究 砒霜 目前，关于癌症影响的信息很少。 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，提供剂量反应数据， 饮用水管理。

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.