title: Polycyclic aromatic hydrocarbons within airborne particulate matter (PM(2.5)) produced DNA bulky stable adducts in a human lung cell coculture model.
abstract: To extend current knowledge on the underlying mechanisms of air pollution particulate matter (PM(2.5))-induced human lung toxicity, the metabolic activation of polycyclic aromatic hydrocarbons (PAH) within PM(2.5) 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(2.5), unlike L132 cells. Particles, inorganic fraction and positive controls [i.e. TiO(2), 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(2.5) induced CYP1A1 gene expression and CYP1A1 catalytic activity in human AM and, thereafter, PAH-DNA bulky stable adduct formation. Adduct spots in PM(2.5) -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(2.5) induced CYP1A1 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(2.5) or PM(2.5), 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.
authors.affiliation: Université Lille Nord de France, Lille, France.
authors.forename: Imane
authors.initials: I
authors.lastname: Abbas
authors.forename: Guillaume
authors.initials: G
authors.lastname: Garçon
authors.forename: Françoise
authors.initials: F
authors.lastname: Saint-Georges
authors.forename: Véronique
authors.initials: V
authors.lastname: Andre
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.forename: Sylvain
authors.initials: S
authors.lastname: Billet
authors.forename: Jérémie Le
authors.initials: JL
authors.lastname: Goff
authors.forename: Anthony
authors.initials: A
authors.lastname: Verdin
authors.forename: Philippe
authors.initials: P
authors.lastname: Mulliez
authors.forename: François
authors.initials: F
authors.lastname: Sichel
authors.forename: Pirouz
authors.initials: P
authors.lastname: Shirali
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D002460:Cell Line; D018920:Coculture Techniques; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018736:DNA Adducts; D004784:Environmental Monitoring; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005602:France; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009153:Mutagens / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D013499:Surface Properties
chemical_list: D000393:Air Pollutants; D018736:DNA Adducts; D009153:Mutagens; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1