title: Mutagenicity and genotoxicity of PM2.5 issued from an urbano-industrialized area of Dunkerque (France).
abstract: Epidemiological studies have demonstrated the link between chronic exposure to particulate matter (PM), especially particles with an aerodynamic diameter lesser than 2.5 µm (PM(2.5) ), and lung cancer. Mechanistic investigations focus on the contribution of the various genotoxicants adsorbed onto the particles, and more particularly on polycyclic aromatic hydrocarbons or nitroaromatics. Most of the previous studies dealing with genotoxic and/or mutagenic measurements were performed on organic extracts obtained from PM(2.5) collected in polluted areas. In contrast, we have evaluated genotoxic and mutagenic properties of urbano-industrial PM(2.5) (PM) collected in Dunkerque (France). Thermally desorbed PM(2.5) (dPM) was also comparatively studied. Suspensions of PM and dPM (5-50 µg per plate) were tested in Salmonella tester strains TA98, TA102 and YG1041 ± S9mix. Significant mutagenicity was observed for PM in YG1041 ± S9 mix. In strain TA102 - S9mix, a slight, but not significant dose-response increase was observed, for both PM and dPM. Genotoxic properties of PM and dPM were evaluated by the measurement of (1) 8-OHdG in A549 cells and (2) bulky DNA adducts on A549 cells and on human alveolar macrophages (AMs) in primary culture. A dose-dependant formation of 8-OHdG adducts was observed on A549 cells for PM and dPM, probably mainly attributed to the core of the particles. Bulky DNA adducts were observed only in AMs after exposure to PM and dPM. In conclusion, using relevant exposure models, suspension of PM(2.5) induces a combination of DNA-interaction mechanisms, which could contribute to the induction of lung cancer in exposed populations.
authors.affiliation: Groupe Régional d'Etudes sur le Cancer (GRECAN) EA1772 et IFR 146 (ICORE), Université de Caen Basse-Normandie et Centre François Baclesse, Caen, France. veronique.andre@unicaen.fr
authors.forename: V
authors.initials: V
authors.lastname: André
authors.forename: S
authors.initials: S
authors.lastname: Billet
authors.forename: D
authors.initials: D
authors.lastname: Pottier
authors.forename: J
authors.initials: J
authors.lastname: Le Goff
authors.forename: I
authors.initials: I
authors.lastname: Pottier
authors.forename: G
authors.initials: G
authors.lastname: Garçon
authors.forename: P
authors.initials: P
authors.lastname: Shirali
authors.forename: F
authors.initials: F
authors.lastname: Sichel
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D018736:DNA Adducts / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005602:France; D006801:Humans; D007221:Industry; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009994:Osmolar Concentration; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D014507:Urbanization
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D052638:Particulate Matter; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine