Evaluation of PM2.5 Oxidative Potential (OP) as a proxy for the aerosol toxicity

空气中直径小于2.5微米的微小粉尘颗粒(称为PM2.5)被广泛认为对人体健康有害。发达国家对室外空气中PM2.5的质量浓度进行了严格的监管。暴露在高浓度PM2.5中会导致各种健康问题，包括肺功能下降、哮喘加重，以及患有心脏病或肺病的人过早死亡。到目前为止，这些颗粒对人类造成毒性的机制尚不清楚。最近的研究重点是PM2.5通过产生氧化剂来破坏细胞的能力。然而，PM2.5的氧化电位(OP)和毒性之间的相关性还没有被探索。该项目的目标是解决这一知识差距。为了实现这一目标，PI将测量从世界各地许多污染地点收集的大量PM2.5样本的OP。我们将利用统计学和机械学的方法来揭示PM2.5 OP在诱导细胞毒性中的作用。该项目的成功完成将通过发展新的基础知识来确定和瞄准PM2.5的最大毒害源，从而造福社会。将通过学生研究、培训和公众宣传进一步造福社会。这将包括从代表性不足的群体中招聘和指导本科生，以及开发关于PM2.5毒性的虚拟实验室和教程材料，供在美国地球物理联合会(AGU)地球健康部分会议期间公开传播。许多流行病学研究表明，PM2.5浓度与人类与呼吸系统和心血管系统有关的疾病之间存在密切联系。然而，这些关联强度的时空变异性表明，PM2.5的整体质量浓度并不是气溶胶毒性的最佳替代品。最近的研究表明，与室外空气中PM2.5的质量浓度相比，环境中PM2.5产生氧化剂的能力-称为氧化势(OP)-可能是一个更相关的毒性指标。然而，颗粒OP、细胞毒性和健康终点之间的关系仍然难以捉摸。该项目的目标是促进我们对环境中PM2.5的有机污染物与其细胞毒性之间关系的基本理解。为了实现这一目标，PI将把OP检测的结果与从世界各地许多国家收集的大量PM2.5样本的细胞毒性观察结果进行比较。将富含抗氧化剂的细胞暴露在环境PM2.5样品中的新方法将为评估颗粒驱动的氧化剂生成在诱导细胞毒性中的作用提供最直接的证据。将这种方法与成熟的化学分析方法进行比较，可以评估诱发毒性与测量到的颗粒物OP之间的关系。该项目的成功完成对空气污染管理具有潜在的变革影响，通过发展新的知识和洞察力，将能够使用颗粒物OP作为气溶胶毒性的替代指标。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Small airborne dust particles smaller than 2.5 micrometers in size (known as PM2.5) are widely recognized as detrimental to human health. The mass concentrations of PM2.5 in outdoor air are highly regulated in developed nations. Exposure to high concentrations of PM2.5 can cause various health problems including decreased lung function, aggravated asthma, and premature death in people with heart or lung disease. To date, the mechanisms by which these particles induce toxicity in humans are not well understood. Recent work has focused on the ability of PM2.5 to damage cells through the production of oxidants. However, the correlation between the oxidative potential (OP) and toxicity of PM2.5 has not been explored. The goal of this project is to address this knowledge gap. To achieve this goal, the PI will measure the OP of a large number of samples of PM2.5 collected across many polluted sites around the world. Both statistical and mechanistic approaches will be utilized to unravel the role of PM2.5 OP in inducing cellular toxicity. The successful completion of this project will benefit society through the development of new fundamental knowledge to identify and target the most toxic sources of PM2.5. Further benefits to society will be achieved through student research training and public outreach. This will include the recruitment and mentoring of undergraduate students from under-represented groups along with the development of virtual labs and tutorial materials on PM2.5 toxicity for public dissemination during meetings of the GeoHealth section of the American Geophysical Union (AGU). Numerous epidemiological studies have shown strong linkages between PM2.5 concentrations and human diseases related to respiratory and cardiovascular systems. However, the spatiotemporal variability in the strengths of these associations suggests that bulk PM2.5 mass concentration is not the best surrogate of aerosol toxicity. Recent investigations have indicated that the capability of ambient PM2.5 to generate oxidants – known as oxidative potential (OP), might be a more relevant indicator of toxicity than PM2.5 mass concentration in outdoor air. However, the relationships between particle OP, cellular toxicity, and health endpoints have remained elusive. The goal of this project is to advance our fundamental understanding of the relationships between the OP of ambient PM2.5 and their cellular toxicity. To achieve this goal, the PI will compare the results of OP assays with observed cellular toxicity of a large number of PM2.5 samples collected from many countries across the world. The novel approach of exposing antioxidant-enriched cells to ambient PM2.5 samples will provide the most direct evidence for assessing the role of particle-driven oxidant generation in inducing cellular toxicity. Comparison of this approach to well-established chemical assays will allow the assessment of how induced toxicity is related to measured particle OP. Successful completion of this project has potential for transformative impact in air pollution management through the development of new knowledge and insight that will enable the use of particle OP as a proxy for aerosol toxicity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.