BIOMARKERS OF EXPOSURE AND EFFECT IN A TRAFFIC EXPOSED POPULATION

描述（由申请人提供）：可归因于交通和其他燃烧源的颗粒物（PM）与心脏相关健康结局、呼吸系统疾病、肺癌和总体死亡率相关。动物和人类的实验证据表明，暴露于交通相关的PM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，确切的机制是不明确的，并没有很好地表征在大的“现实世界”的人口。我们建议前瞻性地描述个人暴露于汽车尾气的特征，同时在卡车运输业颗粒物研究（一项正在进行的国家流行病学和暴露评估研究）的亚群中重复采集血液和尿液样本。我们将评估测量的暴露与暴露的生物标志物以及氧化和炎症效应之间的关系。具体而言，我们将测量1，2-萘醌和1，4-萘醌白蛋白加合物和尿萘酚（交通相关暴露的生物标志物）的血清水平和C-反应蛋白、白介素-6和可溶性细胞间粘附分子-1的血清水平以及8-羟基-2 '-脱氧鸟苷（效应生物标志物）的尿水平，同时测量暴露。暴露测量将包括元素碳、萘和结合多环芳烃（PAH），这是一种新的附着在元素碳颗粒上的多环芳烃特异性指标，可以将其浓缩并运输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，以识别在车辆尾气暴露中差异激活的基因和基因网络。我们预计，该项目的结果将提供新的和全面的见解，正常的生物反应，汽车尾气，相关的病原体的曝光，并将进一步我们了解这些过程中牵连的肺癌和心脏病的发展。这些问题是非常重要的公共卫生，由于大部分的普通人群暴露于汽车尾气每天的基础上。此外，我们提出的目标与NIEHS环境基因组计划（EGP）的目标一致，以提高对人类遗传易感性的理解。公共卫生相关性：可归因于交通和其他燃烧源的颗粒物（PM）与心脏相关的健康结果、呼吸系统疾病、肺癌和总体死亡率相关。我们预计，该项目的结果将提供新的和全面的见解，正常的生物反应，汽车尾气，相关的病原体的曝光，并将进一步我们了解这些过程中牵连的肺癌和心脏病的发展。这些问题是非常重要的公共卫生，由于大部分的普通人群暴露于汽车尾气每天的基础上。

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.