Polycyclic aromatic hydrocarbons within airborne particulate matter (PM2.5) produced DNA bulky stable adducts in a human lung cell coculture model. Issue 2 (13th September 2011)

• Record Type: Journal Article
• Authors: Abbas, Imane; Garçon, Guillaume; Saint‐Georges, Françoise; Andre, Véronique; Gosset, Pierre; Billet, Sylvain; Goff, Jérémie Le; Verdin, Anthony; Mulliez, Philippe; Sichel, François; Shirali, Pirouz
• Is Part Of: Journal of applied toxicology. Volume 33:Issue 2(2013)
• Page Start: 109
• Page End: 119
• Publication Date: 2011-09-13
• Subjects: Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.1722
• Languages: English
• ISSNs: 0260-437X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>To extend current knowledge on the underlying mechanisms of air pollution particulate matter (PM<sub>2.5</sub>)‐induced human lung toxicity, the metabolic activation of polycyclic aromatic hydrocarbons (PAH) within PM<sub>2.5</sub> and PAH–DNA bulky stable adduct patterns in human alveolar macrophage (AM) and/or human lung epithelial L132 cells in mono‐ and cocultures were studied. In the coculture system, only human AM were exposed to air pollution PM<sub>2.5</sub>, unlike L132 cells. Particles, inorganic fraction and positive controls [i.e. TiO<sub>2</sub>, thermally desorbed PM (dPM) and benzo[a]pyrene, B[a]P, respectively] were included in the experimental design. Cytochrome P450 (CYP) 1A1 gene expression, CYP1A1 catalytic activity and PAH–DNA bulky stable adducts were studied after 24, 48 and/or 72 h. Relatively low doses of PAH within PM<sub>2.5</sub> induced <italic>CYP1A1</italic> gene expression and CYP1A1 catalytic activity in human AM and, thereafter, PAH–DNA bulky stable adduct formation. Adduct spots in PM<sub>2.5</sub>‐exposed human AM were higher than those in dPM‐exposed ones, thereby showing the incomplete removal of PAH by thermal desorption. PAH within air pollution PM<sub>2.5</sub> induced <italic>CYP1A1</italic> gene expression but not CYP1A1 catalytic activity in L132 cells. However, despite the absence of PAH–DNA bulky stable adduct in L132 cells from human AM/L132 cell cocultures exposed to dPM<sub>2.5</sub> or PM<sub>2.5</sub>, reliable quantifiable PAH–DNA bulky stable adducts were observed in L132 cells from human AM/L132 cell coculture exposed to B[a]P. Taken together, these results support the exertion of genotoxicity of highly reactive B[a]P‐derived metabolites produced within human AM not only in primary target human AM, but also in secondary target L132 cells. Copyright © 2011 John Wiley & Sons, Ltd.</p> </abstract>