Validation of Biomarkers in Humans Exposed to PAHs

描述（由申请人提供）： 多环芳烃（PAHs）是一种广泛存在于环境中的有机污染物 由于不完全燃烧的重要贡献， 化石燃料和其他有机材料。接触多环芳烃与 在职业环境中患有肺癌和皮肤癌， 在低环境水平下暴露于多环芳烃的人类患癌症的风险现在变得越来越高， 一个主要的公众关注。为了解决这个问题，各种 已经开发了生物标志物来指示暴露水平或生物学特征。 PAH的影响。然而，其应用的有效性在风险 对低水平多环芳烃的评估是不确定的。这项研究主要将 专注于在中国人群中验证这些生物标志物， 暴露于多环芳烃。待验证的生物标志物包括尿 1-羟基芘、DNA和蛋白质（血红蛋白和白蛋白）加合物以及 p53蛋白。此外，包括CYP 1A 1， 微粒体环氧化物水解酶（mEH）、GSTM 1和p53基因将被鉴定 来评估基因与环境的相互作用。为此，我们会进行一项 研究包括5个项目。本研究的具体目的是：（1） 确定这些候选标记是否能够至少可靠地检测差异 暴露水平相对较高的工人和未暴露的工人之间的差异 受试者;（2）检查这些生物标志物的再现性，并评估 其个体间和个体内变异;（3）估计有效的 暴露标记物的半衰期，并评价它们是否与 最新的暴露或一段时间内的综合暴露;（4） 确定这些标记是否可以可靠地用于区分 未暴露受试者和低环境水平下暴露受试者， 表征其应答关系;（5）调查 这些生物标志物的特异性并确定一般情况下可能产生的影响 混杂因素，如吸烟、饮食、年龄和性别， （6）探讨CYP 1A 1、GSTM 1、mEH、 和p53与多环芳烃暴露的相互作用 生物标志物。这项研究的最终目的是确定是否 这些生物标志物可用作人类风险评估的标志物 在未来大规模流行病学中暴露于低环境水平的PAHs 问题研究

DESCRIPTION (provided by applicant): Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants due to significant contributions from incomplete combustion of fossil fuels and other organic materials. Exposure to PAHs has been associated with lung and skin cancer in occupational setting and a potential increased risk of cancer in humans exposed to PAHs at low ambient levels is now becoming a major public concern. In order to address this problem, a variety of biomarkers have been developed to index the exposure levels or biological effects of PAHs. However, the validity of their applications in risk assessment of PAHs at low levels is uncertain. This proposed study will mainly focus on validating these biomarkers in a Chinese population with broad ranges of exposures to PAHs. The biomarkers to be validated include urinary 1-hydroxypyrene, DNA and protein (hemoglobin and albumin) adducts as well as p53 protein. In addition, the polymorphisms of genes, including CYP1A1, microsomal epoxide hydrolase (mEH), GSTM1, and p53 genes, will be identified to assess gene-environment interactions. For this purpose, we will conduct a study with 5 projects included. The specific aims of this study are: (1) to determine if these candidate markers can at least reliably detect differences between workers with relatively high levels of exposure and unexposed subjects; (2) to examine the reproducibility of these biomarkers and to assess their inter-and intra-individual variabilities; (3) to estimate the effective half-lives of the exposure markers and to evaluate whether they relate to the most current exposure or to integrated exposures over a period of time; (4) to determine whether these markers can be reliably used to differentiate between unexposed subjects and exposed subjects at low ambient levels and to characterize their exposure-response relationships; (5) to investigate the specificity of these biomarkers and to identify possible effects of general confounding factors, such as smoking, diet, age, and gender on the levels of these markers; (6) To evaluate how gene polymorphisms of CYP1A1, GSTM1, mEH, and p53 interact with PAHs exposure in relation to the levels of all candidate biomarkers. The ultimate goal of this study is to determine whether or not these biomarkers can be useful as markers for risk assessment in humans exposed to PAHs at low ambient levels in future large scale epidemiological studies.