title: Inhibition of the formation of benzo[a]pyrene adducts to DNA in A549 lung cells exposed to mixtures of polycyclic aromatic hydrocarbons.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants, which exhibit carcinogenic properties especially in lungs. In the present work, we studied the effect of mixtures of 12 PAHs on the A549 alveolar cells. We first assess the ability of each PAH at inducing gene expression of phase I metabolization enzymes and at generating DNA adducts. A good correlation was found between these two endpoints. We then exposed cells to either binary mixtures of the highly genotoxic benzo[a]pyrene (B[a]P) with each PAH or complex mixtures of all studied PAHs mimicking by real emissions including combustion of wood, cigarette smoke, and atmospheres of garage, silicon factory and urban environments. Compared to pure B[a]P, both types of mixtures led to reduced CYP450 activity measured by the EROD test. A similar trend was observed for the formation of DNA adducts. Surprisingly, the complex mixtures were more potent than B[a]P used at the same concentration for the induction of genes coding for CYP. Our results stress the lack of additivity of the genotoxic properties of PAH in mixtures. Interestingly, an opposite synergy in the formation of B[a]P adducts were observed previously in hepatocytes. Our data also show that measurement of the metabolic activity rather than quantification of gene expression reflects the actual bioactivation of PAHs into DNA damaging species.
authors.affiliation: Univ. Grenoble Alpes, INAC, LCIB, LAN, F-38000, Grenoble, France; CEA, INAC, SyMMES, LAN, F-38000, Grenoble, France; Equipe EPSP Environnement et Prédiction de la Santé des Populations-laboratoire TIMC (UMR CNRS 5525), CHU de Grenoble, Université Grenoble Alpes, UFR de Médecine, Domaine de la Merci, 38706, La Tronche, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Genies
authors.affiliation: Univ. Grenoble Alpes, INAC, LCIB, LAN, F-38000, Grenoble, France; CEA, INAC, SyMMES, LAN, F-38000, Grenoble, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Jullien
authors.affiliation: Univ. Grenoble Alpes, INAC, LCIB, LAN, F-38000, Grenoble, France; CEA, INAC, SyMMES, LAN, F-38000, Grenoble, France; Equipe EPSP Environnement et Prédiction de la Santé des Populations-laboratoire TIMC (UMR CNRS 5525), CHU de Grenoble, Université Grenoble Alpes, UFR de Médecine, Domaine de la Merci, 38706, La Tronche, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lefebvre
authors.affiliation: Univ. Grenoble Alpes, INAC, LCIB, LAN, F-38000, Grenoble, France; CEA, INAC, SyMMES, LAN, F-38000, Grenoble, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Revol
authors.affiliation: Equipe EPSP Environnement et Prédiction de la Santé des Populations-laboratoire TIMC (UMR CNRS 5525), CHU de Grenoble, Université Grenoble Alpes, UFR de Médecine, Domaine de la Merci, 38706, La Tronche, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Maitre
authors.affiliation: Univ. Grenoble Alpes, INAC, LCIB, LAN, F-38000, Grenoble, France; CEA, INAC, SyMMES, LAN, F-38000, Grenoble, France. Electronic address: thierry.douki@cea.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
mesh_terms: D000072283:A549 Cells; D002273:Carcinogens / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D018736:DNA Adducts; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012906:Smoke; D014026:Nicotiana; D001335:Vehicle Emissions; D014934:Wood
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D012906:Smoke; D001335:Vehicle Emissions; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: DNA adducts; Genotoxicity; Metabolism; Mixtures; Polycyclic aromatic hydrocarbons