title: In vitro short-term exposure to air pollution PM2.5-0.3 induced cell cycle alterations and genetic instability in a human lung cell coculture model.
abstract: Although its adverse health effects of air pollution particulate matter (PM2.5) are well-documented and often related to oxidative stress and pro-inflammatory response, recent evidence support the role of the remodeling of the airway epithelium involving the regulation of cell death processes. Hence, the overarching goals of the present study were to use an in vitro coculture model, based on human AM and L132 cells to study the possible alteration of TP53-RB gene signaling pathways (i.e. cell cycle phases, gene expression of TP53, BCL2, BAX, P21, CCND1, and RB, and protein concentrations of their active forms), and genetic instability (i.e. LOH and/or MSI) in the PM2.5-0.3-exposed coculture model. PM2.5-0.3 exposure of human AM from the coculture model induced marked cell cycle alterations after 24h, as shown by increased numbers of L132 cells in subG1 and S+G2 cell cycle phases, indicating apoptosis and proliferation. Accordingly, activation of the TP53-RB gene signaling pathways after the coculture model exposure to PM2.5-0.3 was reported in the L132 cells. Exposure of human AM from the coculture model to PM2.5-0.3 resulted in MS alterations in 3p chromosome multiple critical regions in L132 cell population. Hence, in vitro short-term exposure of the coculture model to PM2.5-0.3 induced cell cycle alterations relying on the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation and genetic instability.
authors.affiliation: Université de Lille, Lille, France; EA4492-UCEIV, Université du Littoral-Côte d'Opale, Dunkerque, France; Lebanese Atomic Energy Commission - CNRS, Beirut, Lebanon.
authors.forename: Imane
authors.initials: I
authors.lastname: Abbas
authors.affiliation: Université de Lille, Lille, France; EA4492-UCEIV, Université du Littoral-Côte d'Opale, Dunkerque, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Verdin
authors.affiliation: Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire, Lille, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.affiliation: Université de Lille, Lille, France; Groupement Hospitalier de l'Institut Catholique de Lille, Lille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Saint-Georges
authors.affiliation: Université de Lille, Lille, France; Centre Commun de Mesures, Université du Littoral-Côte d'Opale, Dunkerque, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cazier
authors.affiliation: Université de Lille, Lille, France; Groupement Hospitalier de l'Institut Catholique de Lille, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mulliez
authors.affiliation: Université de Lille, Lille, France; EA4492-UCEIV, Université du Littoral-Côte d'Opale, Dunkerque, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Courcot
authors.affiliation: Université de Lille, Lille, France; EA4492-UCEIV, Université du Littoral-Côte d'Opale, Dunkerque, France.
authors.forename: Pirouz
authors.initials: P
authors.lastname: Shirali
authors.affiliation: Université de Lille, Lille, France; Groupement Hospitalier de l'Institut Catholique de Lille, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: Université de Lille, Lille, France; EA4492-UCEIV, Université du Littoral-Côte d'Opale, Dunkerque, France; EA4483-IMPECS, Université de Lille 2, Lille, France. Electronic address: guillaume.garcon@univ-lille2.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Garçon
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D008168:Lung / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Air pollution particulate matter; Cell cycle; Coculture model; Genetic instability; Human alveolar macrophage; L132 cells; TP53/RB gene signaling pathway