Search

ABSTRACT Airborne particulate matter (PM) toxicity is of growing interest as diesel exhaust particles have been classified as carcinogenic to humans. However, PM is a mixture of chemicals, and respective contribution of organic and inorganic fractions to PM toxicity remains unclear. Thus, we analysed the link between chemical composition of PM samples and bulky DNA adduct formation supported by CYP1A1 and 1B1 genes induction and catalytic activities. We used six native PM samples, collected in industrial, rural or urban areas, either during the summer or winter, and carried out our experiments on the human bronchial epithelial cell line BEAS-2B. Cell exposure to PM resulted in CYP1A1 and CYP1B1 genes induction. This was followed by an increase in EROD activity, leading to bulky DNA adduct formation in exposed cells. Bulky DNA adduct intensity was associated to global EROD activity, but this activity was poorly correlated with CYPs mRNA levels. However, EROD activity was correlated with both metal and polycyclic aromatic hydrocarbon (PAH) content. Finally, principal components analysis revealed three clusters for PM chemicals, and suggested synergistic effects of metals and PAHs on bulky DNA adduct levels. This study showed the ability of PM samples from various origins to generate bulky DNA adducts in BEAS-2B cells. This formation was promoted by increased expression and activity of CYPs involved in PAHs activation into reactive metabolites. However, our data highlight that bulky DNA adduct formation is only partly explained by PM content in PAHs, and suggest that inorganic compounds, such as iron, may promote bulky DNA adduct formation by supporting CYP activity. Copyright © 2013 John Wiley & Sons, Ltd. [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]