BIOMARKERS OF EXPOSURE AND EFFECT IN A TRAFFIC EXPOSED POPULATION

描述(申请人提供)：交通和其他燃烧来源的颗粒物(PM)与心脏相关的健康结果、呼吸系统疾病、肺癌和总死亡率有关。动物和人类的实验证据表明，暴露于与交通相关的PM会导致全身炎症、氧化应激和细胞周期失调，以及直接的遗传毒性。然而，精确的机制并未得到很好的定义，也没有在大量的“真实世界”人群中得到很好的描述。我们建议前瞻性地描述个人接触汽车尾气的特征，同时同时在卡车行业颗粒研究的一个子群中收集重复的血液和尿液样本，这是一项正在进行的全国性流行病学和暴露评估研究。我们将评估测量的暴露和暴露的生物标记物与氧化和炎症效应之间的关系。具体地说，我们将同时测量血清1，2-萘醌和1，4-萘醌白蛋白加合物和尿酚的水平(交通相关暴露的生物标志物)，以及血清C反应蛋白、白细胞介素6和可溶性细胞间黏附分子-1的水平，以及尿8-羟基-2‘-脱氧鸟苷的水平(影响的生物标志物)。暴露测量将包括元素碳、萘和结合的多环芳烃(PAH)，这是附着在元素碳颗粒上的多环芳烃的一种新的特定指示剂，可以浓缩它们并将其输送到肺部和内脏的目标区域。最后，我们将使用全血RNA进行全基因组基因表达微阵列分析，以识别因汽车尾气暴露而差异激活的基因和基因网络。我们期待这个项目的结果将为汽车尾气的正常生物反应、暴露的相关病因学提供新的和全面的见解，并将进一步了解与肺癌和心脏病的发展有关的过程。这些问题对公共卫生非常重要，因为有很大比例的一般人口每天接触汽车尾气。此外，我们建议的目标与NIEHS环境基因组计划(EGP)的目标一致，即提高对人类对环境暴露的遗传易感性的理解与公共健康相关：交通和其他燃烧来源的颗粒物(PM)与心脏相关的健康结果、呼吸系统疾病、肺癌和总死亡率有关。我们期待这个项目的结果将为汽车尾气的正常生物反应、暴露的相关病因学提供新的和全面的见解，并将进一步了解与肺癌和心脏病的发展有关的过程。这些问题对公共卫生非常重要，因为有很大比例的一般人口每天接触汽车尾气。

DESCRIPTION (provided by applicant): Particulate matter (PM) attributable to traffic and other combustion sources has been associated with cardiac- related health outcomes, respiratory disease, lung cancer, and overall mortality. Experimental evidence in animals and humans suggests that exposure to traffic-related PM results in systemic inflammation, oxidative stress and cell cycle dysregulation, as well as direct genotoxicity. However, the precise mechanisms are poorly defined and have not been well characterized in large "real-world" populations. We propose to prospectively characterize personal exposures to vehicle exhaust while concurrently collecting repeated blood and urine samples in a subpopulation of the Trucking Industry Particle Study, an ongoing national epidemiologic and exposure assessment study. We will assess relationships between measured exposures and biomarkers of exposure and oxidative and inflammatory effects. Specifically we will measure serum levels of 1, 2 naphthoquinone and 1, 4-naphthoquinone albumin adducts and urinary naphthols (biomarkers of traffic- related exposure) and serum levels of C-reactive protein, interleukin-6 and soluble intercellular adhesion molecule-1 and urine levels of 8-hydroxy-2'-deoxyguanosine (biomarkers of effect) with concurrent exposure measurements. Exposure measurements will include elemental carbon, naphthalene, and bound polycyclic aromatic hydrocarbons (PAH), a novel specific indicator of PAHs attached to elemental carbon particles that can concentrate and transport them into the target areas of the lungs and internal organs. Finally, we will perform genome-wide gene expression micro array analysis using whole blood RNA to identify genes and gene networks that are differentially activated in response to vehicle exhaust exposure. We anticipate that the results of this project will provide novel and comprehensive insights into the normal biologic response to vehicle exhaust, the relevant etiologic agents of exposure, and will further our understanding of those processes implicated in the development of lung cancer and heart disease. These issues are of great public health importance due to the large proportion of the general population exposed to vehicle exhaust on a daily basis. Furthermore, our proposed aims are consistent with the goals of NIEHS Environmental Genome Project (EGP) to improve understanding of human genetic susceptibility to environmental exposures PUBLIC HEALTH RELEVANCE: Particulate matter (PM) attributable to traffic and other combustion sources has been associated with cardiac- related health outcomes, respiratory disease, lung cancer, and overall mortality. We anticipate that the results of this project will provide novel and comprehensive insights into the normal biologic response to vehicle exhaust, the relevant etiologic agents of exposure, and will further our understanding of those processes implicated in the development of lung cancer and heart disease. These issues are of great public health importance due to the large proportion of the general population exposed to vehicle exhaust on a daily basis.