ENEA Research Centre of Bologna Division of Models and Technology for Risk Reduction, Laboratory of Atmospheric Pollution, Via Martiri di Monte Sole 4, 40129, Bologna, Italy; Deptartment of Earth and Environmental Sciences, Polaris Research Centre University of Milano-Bicocca, Piazza Della Scienza 1, 20126, Milan, Italy.
Department of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
Chemosphere. 2024 Oct;366:143417. doi: 10.1016/j.chemosphere.2024.143417. Epub 2024 Sep 28.
Air pollution and particulate matter (PM) are the leading environmental cause of death worldwide. Exposure limits have lowered to increase the protection of human health; accordingly, it becomes increasingly important to understand the toxicological mechanisms on cellular models at low airborne PM concentrations which are relevant for actual human exposure. The use of air liquid interface (ALI) models, which mimic the interaction between airborne pollutants and lung epithelia, is also gaining importance in inhalation toxicological studies. This study reports the effects of ALI direct exposure of bronchial epithelial cells BEAS-2B to ambient PM (i.e. particles with aerodynamic diameter lower than 1 μm). Gene expression (HMOX, Cxcl-8, ATM, Gadd45-a and NQO1), interleukin (IL)-8 release, and DNA damage (Comet assay) were evaluated after 24 h of exposure. We report the dose-response curves of the selected toxicological outcomes, together with the concentration-response association and we show that the two curves differ for specific responses highlighting that concentration-response association may be not relevant for understanding toxicological outcomes. Noteworthy, we show that pro-oxidant effects may be driven by the deposition of freshly emitted particles, regardless of the airborne PM mass concentration. Furthermore, we show that reference airborne PM metrics, namely airborne mass concentration, may not always reflect the toxicological process triggered by the aerosol. These findings underscore the importance of considering different aerosol metrics to assess the toxicological potency of fine and ultrafine particles. To better protect human health additional metrics should be defined, than account for the properties of the entire aerosol mixture including specific as particle size (i.e. particles with aerodynamic diameter lower than 20 nm), the relevant aerosol sources (e.g., traffic combustion, secondary organic aerosol …) as well as their atmospheric processing (freshly emitted vs aged ones).
空气污染和颗粒物（PM）是全球主要的环境死因。暴露限值已经降低，以增加对人类健康的保护；因此，了解与实际人类暴露相关的低空 PM 浓度下细胞模型的毒理学机制变得越来越重要。空气-液体界面（ALI）模型的使用也在吸入毒理学研究中变得越来越重要，该模型模拟了空气传播污染物与肺上皮之间的相互作用。本研究报告了大气 PM（即空气动力学直径小于 1μm 的颗粒）直接暴露于支气管上皮细胞 BEAS-2B 的 ALI 对基因表达（HMOX、Cxcl-8、ATM、Gadd45-a 和 NQO1）、白细胞介素（IL）-8 释放和 DNA 损伤（彗星试验）的影响。我们报告了选定毒理学结果的剂量反应曲线，以及浓度反应关联，并表明对于特定的反应，两条曲线不同，这突出表明浓度反应关联可能与理解毒理学结果无关。值得注意的是，我们表明，促氧化剂效应可能是由新排放颗粒的沉积引起的，而与空气中的 PM 质量浓度无关。此外，我们表明，参考空气中的 PM 指标，即空气中的质量浓度，并不总是反映气溶胶引发的毒理学过程。这些发现强调了考虑不同气溶胶指标来评估细颗粒物和超细颗粒的毒理学效力的重要性。为了更好地保护人类健康，应该定义比仅考虑空气传播颗粒的质量浓度更全面的指标，这些指标应考虑整个气溶胶混合物的特性，包括特定的粒径（即空气动力学直径小于 20nm 的颗粒）、相关的气溶胶源（例如交通燃烧、二次有机气溶胶等）以及它们的大气处理（新鲜排放与老化排放）。
