title: Xenobiotic metabolism induction and bulky DNA adducts generated by particulate matter pollution in BEAS-2B cell line: geographical and seasonal influence.
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.
authors.affiliation: Université Lille Nord de France, France; ULCO, UCEIV EA4492, F-59140, Dunkerque, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Lepers
authors.forename: Véronique
authors.initials: V
authors.lastname: André
authors.forename: Mona
authors.initials: M
authors.lastname: Dergham
authors.forename: Sylvain
authors.initials: S
authors.lastname: Billet
authors.forename: Anthony
authors.initials: A
authors.lastname: Verdin
authors.forename: Guillaume
authors.initials: G
authors.lastname: Garçon
authors.forename: Dorothée
authors.initials: D
authors.lastname: Dewaele
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cazier
authors.forename: François
authors.initials: F
authors.lastname: Sichel
authors.forename: Pirouz
authors.initials: P
authors.lastname: Shirali
mesh_terms: D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000096:biosynthesis* / Q000235:genetics; D018736:DNA Adducts / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008670:Metals / Q000032:analysis / Q000633:toxicity*; D015999:Multivariate Analysis; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D012621:Seasons; D013997:Time Factors
chemical_list: D018736:DNA Adducts; D008670:Metals; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: BEAS-2B; Particulate Matter; bulky DNA adducts; emission sources; polycyclic aromatic hydrocarbons metabolism