Validation of Biomarkers in Humans Exposed to PAHs

暴露于 PAH 的人类生物标志物的验证

• 批准号: 6448386
• 负责人: QINGSHAN QU
• 金额: $ 25.2万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6448386
• 关键词: Chinese; albumins; benzopyrenes; biomarker; blood chemistry; cancer risk; carbopolycyclic compound; clearance rate; clinical research; cooperative study; cytochrome P450; diet; environment related neoplasm /cancer; environmental contamination; environmental exposure; gene environment interaction; genetic polymorphism; genetic susceptibility; hemoglobin; human subject; neoplasm /cancer epidemiology; nucleic acid sequence; p53 gene /protein; smoking; urinalysis

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.

描述（由申请人提供）： 多环芳烃（PAHS）是广泛的环境 由于不完整的燃烧而产生的重大贡献，污染物 化石燃料和其他有机材料。暴露于PAHS已关联 在职业环境中肺癌和皮肤癌的潜力增加 在低环境水平上暴露于PAH的人类中癌症的风险现在已成为 一个主要的公众关注。为了解决这个问题，各种各样 已经开发了生物标志物来索引暴露水平或生物学 PAH的影响。但是，其风险申请的有效性 低水平的PAH评估尚不确定。这项拟议的研究将主要是 专注于验证这些生物标志物在中国人群中 对PAH的暴露。要验证的生物标志物包括尿 1-羟基苯乙烯，DNA和蛋白质（血红蛋白和白蛋白）加合物以及 p53蛋白。另外，包括CYP1A1在内的基因的多态性 将鉴定出微粒体环氧化物水解酶（MEH），GSTM1和p53基因 评估基因环境相互作用。为此，我们将进行 包括5个项目的研究。这项研究的具体目的是：（1） 确定这些候选标记是否至少可以可靠地检测到差异 在暴露水平相对较高的工人和未暴露的工人之间 受试者； （2）检查这些生物标志物的可重复性并评估 它们的间和个体差异； （3）估计有效 曝光标记的半衰期，并评估它们是否与 一段时间内，大多数当前的暴露或综合暴露； （4）至 确定这些标记是否可以可靠地用于区分 在低环境水平下未接触的受试者和暴露受试者 表征他们的暴露响应关系； （5）调查 这些生物标志物的特异性并确定一般的可能影响 混杂因素，例如吸烟，饮食，年龄和性别 这些标记； （6）评估CYP1A1，GSTM1，MEH的基因多态性如何 p53与所有候选水平相关的PAHS暴露与PAH相互作用 生物标志物。这项研究的最终目标是确定是否 这些生物标志物可以作为人类风险评估的标记有用 在未来的大规模流行病学中暴露于低环境水平的PAH 研究。