10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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In Vitro Toxicity of PM Collected at Different Sites in Switzerland: Correlation between Chemical Composition and Toxicity
LAURE-ESTELLE CASSAGNES, Zaira Leni, Kaspar Rudolf Dällenbach, Gaëlle Uzu, Andre S.H. Prévôt, Urs Baltensperger, Jean-Luc Jaffrezo, Imad El Haddad, Marianne Geiser, Josef Dommen, Paul Scherrer Institute
Abstract Number: 149 Working Group: Aerosol Toxicology
Abstract Outdoor pollution is estimated to be responsible for more than 4.3 million premature deaths per year worldwide [1]. However, the link between particle properties and different adverse effects is not yet resolved. There is an urgent need to support epidemiological evidence by experiments aimed at determining which particle properties and which biological responses are the most crucial for disease development and susceptibility to air pollution. It has been shown that in the presence of antioxidants, trace metals and organic compounds, like quinones, may induce redox cycling in pulmonary cells and thereby increase reactive oxygen species (ROS) production [2]. We explored the relationship between particulate matter (PM) chemical composition and adverse effects on normal and diseased human airway epithelia at the molecular level with a focus on the interactions of particles with the inner surface of the lungs and the impact of ROS thereon.
Two model compounds were tested: a) copper (CuII) - originating from non-combustion traffic sources - and b) 1,4-naphthoquinone (1,4-NQ) – a surrogate representing redox active organic molecules emitted during combustion or produced by photochemical reactions of polycyclic aromatic hydrocarbons. These were applied to the air liquid interface (ALI) of normal and diseased differentiated human bronchial epithelia (HBE). Then, PM10 and PM2.5 winter and summer filter extracts from urban and rural sites in Switzerland were deposited onto the ALI of HBE cell cultures. For exposure experiments, different biological endpoints including: cytotoxicity, release of (pro) inflammatory mediators (IL6 and IL8) as well as gene expression of selected pathways leading to inflammation, DNA damage, response to oxidative stress, apoptosis and senescence response, were assessed.
In parallel, the oxidative potential (OP) of the filter extracts was estimated by 3 assays: dithiothreitol, DTT; dichlorofluorescein, DCFH ; and ascorbic acid, AA.
1,4-NQ induced a high cytotoxicity, especially in diseased epithelia, while CuII showed less toxicity. The combination of 1,4-NQ and CuII revealed a synergistic effect regarding cytotoxicity and IL8 release. Exposure of filter extracts showed a very high sensitivity of cystic fibrosis epithelia with up to 60% cytotoxicity. The cytotoxicity variability within our dataset will be compared to source apportionment results for the organic aerosols (OA, AMS), to the OP data and to trace metals content (ICP-MS). We will discuss the role played by the PM compounds in the redox cycling at the surface of the lungs as well as the sources responsible for the adverse effects to the bronchial epithelia.
This abstract is funded by the SNF grant CR32I3_166325.
[1] Lelieved J. Clean air in the Anthropocene. Faraday Discuss. 2017;(200), 693-703. [2] Charrier JG, et al. Hydrogen peroxide formation in a surrogate lung fluid by transition metals and quinones present in particulate matter. Environ Sci Technol. 2014;48:7010-7017.