Validation of Biomarkers in Humans Exposed to PAHs

描述(由申请人提供)： 多环芳烃(PAHs)是一种广泛存在的环境污染物 因未完全燃烧而产生的污染物 化石燃料和其他有机材料。与接触多环芳烃有关 有肺癌和皮肤癌的职业背景和潜在的增加 暴露在低环境水平多环芳烃中的人类患癌症的风险现在正在变得 这是公众关注的一个主要问题。为了解决这个问题，各种 已经开发出生物标记物来索引暴露水平或生物 多环芳烃的影响。然而，他们的应用在风险方面的有效性 对低水平多环芳烃的评估是不确定的。这项拟议的研究将主要 重点在中国大范围人群中验证这些生物标志物 暴露在多环芳烃中。需要验证的生物标志物包括尿液 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，包括细胞色素P1A1在内的基因的多态性， 微粒体环氧化物水解酶(Meh)、GSTM1和p53基因将被鉴定 以评估基因与环境的相互作用。为此，我们将进行一项 研究包括5个项目。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差异 接触水平相对较高的工人和未接触者之间 受试者；(2)检查这些生物标志物的重复性并评估 它们的个体间和个体内的变异；(3)估计有效的 暴露标记的半衰期，并评估它们是否与 最新暴露或一段时间内综合暴露；(4) 确定这些标记是否可以可靠地用于区分 未暴露的受试者和暴露在低环境水平和 描述他们的暴露-反应关系；(5)调查 这些生物标志物的特异性，并确定一般情况下可能的影响 令人困惑的因素，如吸烟、饮食、年龄和性别 这些标记；(6)评估CYP1A1、GSTM1、meh、 和P53与PAHs暴露的相互作用与所有候选者的水平有关 生物标志物。这项研究的最终目标是确定 这些生物标志物可以作为人类风险评估的有用标志物。 在未来的大规模流行病学中暴露于低环境水平的多环芳烃 学习。

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.