Cellular effects of subway air particles in human lung cells

项目摘要/摘要 该项目将对费城三个地下地铁站的室内空气质量进行比较 相应的地上城市位置以及一个郊区位置。我们之前发现，首相 费城地铁站的水平可能比城市街道的水平高出五倍。我们会 评估不同地点颗粒物(PM)对肺上皮细胞(16HBE和原代)的影响 细胞)，评估细胞毒性、氧化应激和涉及抗氧化剂的细胞反应途径 反应元件(ARE)和异源反应元件(XRE)。主要目的是评估 各种PM成分对这些细胞反应的贡献。在目标1中，我们将收集102个样本 并确定黑碳(BC)、超细颗粒(UFP)、 金属与细胞效应相关。BC和UFP都与细胞氧化有关 压力。地铁PM中的铁、铜、锑和锌等金属含量特别高，这些金属来自 钢轨、车轮、刹车片和列车的其他部件，它们与氧化应激和 是来自其他PM来源的激活。在目标2中，我们将比较可溶/可螯合金属的作用。 对金属全颗粒对细胞的影响，以及有机化合物对细胞的贡献 这些影响。作为这项工作的一部分，我们将探索XRE的贡献和细胞的途径 通过使用针对相关传感器/转录因子的siRNA、芳烃受体(AhR)和 NRF2。剂量反应曲线将被用来评估一定浓度范围内的影响。结果 将有助于了解并理想地减轻地铁空气颗粒物的健康风险。我们已经组建了一支 多学科研究团队，包括空气颗粒物分析、细胞氧化应激、 统计分析和分析金属分析，以及环保局的吸入毒物学家。该项目包括 十个本科生职位，在维拉诺瓦的三个不同部门工作，两个暑期 环保局实验室的职位。学生将是这部作品的主要推动者，它的解释和展示 出版作品的全国性会议和作者。

PROJECT SUMMARY/ABSTRACT This project will compare indoor air quality at three underground subway stations in Philadelphia with the corresponding aboveground urban locations as well as one suburban location. We found previously that PM levels in Philadelphia subway stations can be up to five times higher than levels on an urban street. We will assess effects of particulate matter (PM) from the various locations on lung epithelial cells (16HBE and primary cells), assessing cytotoxicity, oxidative stress, and the cellular response pathways involving the antioxidant response element (ARE) and the xenobiotic response element (XRE). A primary purpose is to assess the contributions of various PM components to these cellular responses. In Aim 1, we will collect 102 total samples from the various locations and determine to what extent levels of black carbon (BC), ultrafine particles (UFP), and metals correlate with the cellular effects. Both BC and UFP have been associated with cellular oxidative stress. Subway PM is particularly high in metals such as iron, copper, antimony and zinc, which come from the rails, wheels, brake pads, and other parts of the trains, which have been correlated with oxidative stress and ARE activation from other PM sources. In Aim 2, we will examine the role of soluble/chelatable metals compared to metals in whole particles on the cellular effects, as well assess contributions from organic compounds on these effects. As part of this work, we will probe the contributions of the XRE and ARE pathways to the cellular effects by using siRNA against the relevant sensors/transcription factors, aryl hydrocarbon receptor (AhR) and Nrf2, respectively. Dose response curves will be used to assess effects over a range of concentrations. Results will help in understanding and ideally mitigating the health risks of subway air particles. We have assembled a multidisciplinary team of researchers, including experts in air particulate analysis, cellular oxidative stress, statistical analysis, and analytical metal analysis, and an inhalation toxicologist at the EPA. The project includes ten undergraduate student positions working in three different departments at Villanova and two summer positions at an EPA lab. Students will be primary drivers of the work, its interpretation, and presentation at national conferences and authors on published work.