Metabolic Activation of the Organic Fraction Coated-Onto Air Pollution PM_2.5 and its Genotoxicity in a Co-Culture Model of Human Lung Cells

Abstract:

Air pollution Particulate Matter (PM2.5) is described as one of the major risk factors affecting human health. Hence, the objective of our research project was to evaluate the lung toxicity of PM_2.5 collected in Dunkerque (France), through the study of the metabolic activation of its organic fraction (e.g. Polycyclic Aromatic Hydrocarbons, PAHs; Volatile Organic Compounds, VOCs) and its genotoxicity in two human cell models: embryonic lung epithelial L132 cells and Alveolar Macrophages (AM) isolated from bronchiolo-alveolar lavages of healthy outpatients, in mono- and/or coculture. The coculture system we used allowed the direct exposure of AM to PM_2.5, and the interaction between the two cell types only through soluble factor diffusion. Exposure to Dunkerque City’s PM_2.5 induced the gene expression of phase I and phase II enzymes (e.g. CYP1A1, CYP2E1, CYP2F1, NQO1, GST∏1, GSTμ3) involved in the metabolic activation of PAHS and/or VOCS, in AM, in mono- and coculture, and in L132 cells, only in monoculture. Taken together, these results reinforced the key role of AM in lung defenses, and indicated that particles, as physical vector of the penetration and retention of coated-PAHS and/or VOCS within cells, enabled them to exert a durable toxicity. DNA bulky adduct formation was also reported not only in Dunkerque City’s PM_2.5-exposed AM, in mono- and coculture, but also in L132 cells from PAH-exposed coculture. Loss of Heterozygosity (LOH) and/or MicroSatellite Instability (MSI) of some MicroSatellites (MS) located in multiple critical regions of chromosome 3 were reported in L132 cells from Dunkerque City’s PM_2.5-exposed mono- or cocultures.

• Periodical: Advanced Materials Research (Volume 324)
• Pages: 473-476
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.324.473
• Online since: August 2011
• Authors: Imane Abbas, Guillaume Garçon, Sylvain Billet, Anthony Verdin, Fabienne Escande, Françoise Saint-Georges, Philipe Mulliez, Pierre Gosset, Pirouz Shirali
• Keywords: Air Pollution Particulate Matter (PM_2.5), Alveolar Macrophage, Coculture Model, DNA Bulky Adduct, L132 Cell Line, Loss of Heterozygosity, Metabolic Activation, Microsatellite Instability

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