Occurrence of molecular abnormalities of cell cycle in L132 cells after in vitro short-term exposure to air pollution PM2.5 |
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| Authors: | Imane Abbas Guillaume Garçon Françoise Saint-Georges Sylvain Billet Anthony Verdin Pierre Gosset Philippe Mulliez Pirouz Shirali |
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| Institution: | 1. Université Lille Nord de France, Lille, France;2. Unité de Chimie Environnementale et Interactions sur le Vivant (UCEIV), EA4492, Equipe Toxicologie, Université du Littoral-Côte d’Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, Avenue Maurice Schumann, 59140 Dunkerque, France;3. Service de Pneumologie, Hôpital Saint-Philibert, Groupement Hospitalier de l’Institut Catholique de Lille (GHICL)-Faculté Libre de Médecine de Lille (FLM), Rue du Grand But, BP 249, 59462 Lomme Cedex, France;4. Laboratoire d’Anatomie et de Cytologie Pathologique, Hôpital Saint-Vincent, Groupement Hospitalier de l’Institut Catholique de Lille (GHICL)-Faculté Libre de Médecine de Lille (FLM), Rue du Port, 59046 Lille Cedex, France;1. Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, China;2. Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China;3. Leibniz Institute for Age Research–Fritz Lipmann Institute, Jena, Germany;4. Sir Runrun Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China;5. Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;6. Department of Pediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Ministry of Education Key Laboratory of Birth Defects, Sichuan University, Chengdu, China;1. Department of Pediatrics, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Jette, Belgium;2. Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Jette, Belgium;3. Department of Pediatrics, Universitair Ziekenhuis Gent, Ghent, Belgium;1. Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA;2. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA;3. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA;4. Cancer Stem Cell Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA;5. Hematologic Malignancies Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA;6. State Key Laboratory of Experimental Hematology, Institute of Hematology, Tianjin, People''s Republic of China;7. Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People''s Republic of China |
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| Abstract: | To improve the knowledge of the underlying mechanisms implying in air pollution Particulate Matter (PM)-induced lung toxicity in humans, we were interested in the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation in the L132 target human lung epithelial cell model. The most toxicologically relevant physical and chemical characteristics of air pollution PM2.5 collected in Dunkerque, a French highly-industrialized sea-side city, were determined. L132 cells were exposed during 24, 48 and 72 h to Dunkerque City's PM2.5 (i.e. Lethal Concentration (LC)10 = 18.84 μg PM/mL or 5.02 μg PM/cm2; LC50 = 75.36 μg PM/mL or 20.10 μg PM/cm2), TiO2 and desorbed PM (i.e. dPM; EqLC10 = 15.42 μg/mL or 4.11 μg PM/cm2; EqLC50 = 61.71 μg/mL or 16.46 μg PM/cm2), benzene (7 μM) or Benzoa]Pyrene (Ba]P; 1 μM). Dunkerque City's PM2.5 altered the gene expression and/or the protein concentration of several key cell cycle controllers from TP53-RB gene signaling pathway (i.e. P53; BCL2; P21; cyclin D1, cyclin-dependent kinase 1; retinoblastoma protein) in L132 cells, thereby leading to the occurrence of cell proliferation and apoptosis together. The activation of the critical cell cycle controllers under study might be related to PM-induced oxidative stress, through the possible involvement of covalent metals in redox systems, the metabolic activation of organic chemicals by enzyme-catalyzed reactions, and phagocytosis. Taken together, these results might ask the critical question whether there is a balance or, in contrast, rather an imbalance between the cell proliferation and the apoptosis occurring in PM-exposed L132 cells, with possible consequences in term of PM-induced lung tumorgenesis. |
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