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Background: Classified as carcinogenic to humans by the IARC in 2013, fine air particulate matter (PM 2.5 ) can be inhaled and retained into the lung or reach the systemic circulation. This can cause or exacerbate numerous pathologies to which the elderly are often more sensitive., Methods: In order to estimate the influence of age on the development of early cellular epigenetic alterations involved in carcinogenesis, peripheral blood mononuclear cells sampled from 90 patients from three age classes (25-30, 50-55 and 75-80 years old) were ex vivo exposed to urban PM 2.5 ., Results: Particles exposure led to variations in telomerase activity and telomeres length in all age groups without any influence of age. Conversely, P16 INK4A gene expression increased significantly with age after exposure to PM 2.5 . Age could enhance MGMT gene expression after exposure to particles, by decreasing the level of promoter methylation in the oldest people., Conclusion: Hence, our results demonstrated several tendencies in cells modification depending on age, even if all epigenetic assays were carried out after a limited exposure time allowing only one or two cell cycles. Since lung cancer symptoms appear only at an advanced stage, our results underline the needs for further investigation on the studied biomarkers for early diagnosis of carcinogenesis to improve survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Particulate Matter (PM) air pollution is one of the major concerns for environment and health. Understanding the heterogeneity and complexity of fine and ultrafine PM is a fundamental issue notably for the assessment of PM toxicological effects. The aim of this study was to evaluate mutagenicity and cytotoxicity of a multi-influenced urban site PM, with or without the ultrafine fraction. For this purpose, PM 2.5-0.3 (PM with aerodynamic diameter ranging from 0.3 to 2.5 μm) and PM 2.5 were collected in Dunkerque, a French coastal industrial city and were extensively characterized for their physico-chemical properties, including inorganic and organic species. In order to identify the possible sources of atmospheric pollution, specific criteria like Carbon Preference Index (CPI) and PAH characteristic ratios were investigated. Mutagenicity assays using Ames test with TA98, TA102 and YG1041 Salmonella strains with or without S9 activation were performed on native PM sample and PM organic extracts and water-soluble fractions. BEAS-2B cell viability and cell proliferation were evaluated measuring lactate dehydrogenase release and mitochondrial dehydrogenase activity after exposure to PM and their extracts. Several contributing sources were identified in PM: soil resuspension, marine emissions including sea-salt or shipping, road traffic and industrial activities, mainly related to steelmaking or petro-chemistry. Mutagenicity of PM was evidenced, especially for PM 2.5 , including ultrafine fraction, in relation to PAHs content and possibly nitro-aromatics compounds. PM induced cytotoxic effects at relatively high doses, while alteration of proliferation with low PM doses could be related to underlying mechanisms such as genotoxicity. [ABSTRACT FROM AUTHOR]

Compelling evidence indicates that exposure to air pollutionparticulate matter (PM) affects human health. However, how PM compositioninteracts with PM-size to cause adverse health effects needs elucidation.In this study, we were also interested in the physicochemical characteristicsand toxicological end points of PM2.5–0.3samplesproduced in rural, urban, or industrial surroundings, thereby expectingto differentiate their respective in vitroadversehealth effects in human bronchial epithelial cells (BEAS-2B). Physicochemicalcharacteristics of the three PM2.5–0.3samples,notably their inorganic and organic components, were closely relatedto their respective emission sources. Referring also to the dose/responserelationships of the three PM2.5–0.3samples, themost toxicologically relevant exposure times (i.e., 24, 48, and 72h) and doses (i.e., 3.75 μg PM/cm2and 15 μgPM/cm2) to use to study the underlying mechanisms of actioninvolved in PM-induced lung toxicity were chosen. Organic chemicalsadsorbed on the three PM2.5–0.3samples (i.e., polycyclicaromatic hydrocarbons) were able to induce the gene expression ofxenobiotic-metabolizing enzymes (i.e., Cytochrome P4501A1 and 1B1,and, to a lesser extent, NADPH-quinone oxidoreductase-1). Moreover,intracellular reactive oxygen species within BEAS-2B cells exposedto the three PM2.5–0.3samples induced oxidativedamage (i.e., 8-hydroxy-2′-deoxyguanosine formation, malondialdehydeproduction and/or glutathione status alteration). There were alsostatistically significant increases of the gene expression and/orprotein secretion of inflammatory mediators (i.e., notably IL-6 andIL-8) in BEAS-2B cells after their exposure to the three PM2.5–0.3samples. Taken together, the present findings indicated that oxidativedamage and inflammatory response preceeded cytotoxicity in air pollutionPM2.5–0.3-exposed BEAS-2B cells and supported theidea that PM-size, composition, and origin could interact in a complexmanner to determine the in vitroresponsiveness toPM. [ABSTRACT FROM AUTHOR]

Abstract Particulate matter in ambient air constitutes a complex mixture of fine and ultrafine particles composed of various chemical compounds including metals, ions, and organics. A multidisciplinary approach was developed by studying physico-chemical characteristics and mechanisms involved in the toxicity of particulate atmospheric pollution. PM 0.3–2.5 and PM 2.5 including ultrafine particles were sampled in Dunkerque, a French industrialized seaside city. PM samples were characterized from a chemical and toxicological point of view. Physico-chemical characterization evidenced that PM 2.5 comes from several sources: natural ones, such as soil resuspension and marine sea-salt emissions, as well as anthropogenic ones, such as shipping traffic, road traffic, and industrial activities. Human BEAS-2B lung cells were exposed to PM 0.3–2.5 , or to the Extractable Organic Matter (EOM) of PM 0.3–2.5 and PM 2.5. These exposures induced several mechanisms of action implied in the genotoxicity, such as oxidative DNA adducts and DNA Damage Response. The toxicity of PM-EOM was higher for the sample including the ultrafine fraction (PM 2.5) containing also higher concentrations of polycyclic aromatic hydrocarbons. These results evidenced the major role of organic compounds in the toxicity of PM. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]