Genetic and epigenetic alterations in normal and sensitive COPD-diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM 2.5
| Autor: | Bérénice Leclercq, Brice M.R. Appenzeller, Fabrice Nesslany, Véronique Riffault, M. Happillon, Laurent Y. Alleman, Esperanza Perdrix, Jean-Marc Lo-Guidice, Emilie M. Hardy, Guillaume Garçon, Sébastien Anthérieu, Anne Platel, Nathalie Grova, Patrice Coddeville |
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| Přispěvatelé: | Impact de l'environnement chimique sur la santé humaine (IMPECS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Département S.A.G.E (SAGE), École des Mines de Douai (Mines Douai EMD), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Luxembourg Institute of Health (LIH), This work benefited from grants from the ITMO Cancer (i.e., Plan Cancer, 2009–2013, Contract n°ENV201210), the University of Lille, and IMT Lille Douai. BL's PhD is supported by the Région Nord-Pas de Calais and IMT Lille Douai (Contract n°13005131)., The authors would also like to convey their sincere thanks to the Lille University of Health and Law which gave us the opportunity to easily access to the sampling site and skillfully helped us in the setting up of the sampling materials needed to collect air pollution-derived fine particles. They gratefully acknowledge B. MALET for his helpful technical support in the sampling of air pollution-derived particles and in the analyses of metals. They also sincerely thank Dr A. HACHIMI and Dr P-E. LAFARGUE, from MicroPolluants Technologie S.A. (Saint Julien Les Metz, France), for their highly skillful assistance in the analyses of polychlorinated dibenzo-p-dioxin and furans, and dioxin-like and marker polychlorinated biphenyls., Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre for Energy and Environment (CERI EE), Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Centre for Energy and Environment (CERI EE - IMT Nord Europe), Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Nord Europe) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Telomerase MESH: Hypersensitivity Health Toxicology and Mutagenesis Cell MESH: Pulmonary Disease Chronic Obstructive/genetics 010501 environmental sciences Biology Toxicology 01 natural sciences 03 medical and health sciences Histone H3 MESH: Epithelial Cells/drug effects Sensitivity medicine Epigenetics MESH: Particulate Matter/toxicity MESH: Epigenesis Genetic MESH: Toxicity Tests 0105 earth and related environmental sciences Genetics Healthy and COPD phenotypes MESH: Humans MESH: Air Pollutants/analysis General Medicine MESH: Air Pollutants/toxicity MESH: Particulate Matter/analysis MESH: Air Pollution/analysis Pollution 3. Good health Telomere MESH: Cell Line 030104 developmental biology medicine.anatomical_structure Cell culture Genetic and epigenetic hallmarks [SDV.TOX]Life Sciences [q-bio]/Toxicology Cancer research H3K4me3 Air pollution-derived PM(2.5) Human bronchial epithelial cells DNA hypomethylation |
| Zdroj: | Environmental Pollution Environmental Pollution, Elsevier, 2017, 230 (1), pp.163-177. ⟨10.1016/j.envpol.2017.06.028⟩ Environmental Pollution, 2017, 230 (1), pp.163-177. ⟨10.1016/j.envpol.2017.06.028⟩ |
| ISSN: | 0269-7491 1873-6424 |
| Popis: | International audience; Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface. Thereafter, they were repeatedly exposed to air pollution-derived PM2.5 to study the occurrence of some relevant genetic and/or epigenetic endpoints. Concentration-, exposure- and season-dependent increases of OH-B[a]P metabolites in NHBE, and to a lesser extent, COPD-DHBE cells were reported; however, there were more tetra-OH-B[a]P and 8-OHdG DNA adducts in COPD-DHBE cells. No increase in primary DNA strand break nor chromosomal aberration was observed in repeatedly exposed cells. Telomere length and telomerase activity were modified in a concentration- and exposure-dependent manner in NHBE and particularly COPD-DHBE cells. There were a global DNA hypomethylation, a P16 gene promoter hypermethylation, and a decreasing DNA methyltransferase activity in NHBE and notably COPD-DHBE cells repeatedly exposed. Changes in site-specific methylation, acetylation, and phosphorylation of histone H3 (i.e., H3K4me3, H3K9ac, H3K27ac, and H3S10ph) and related enzyme activities occurred in a concentration- and exposure-dependent manner in all the repeatedly exposed cells. Collectively, these results highlighted the key role played by genetic and even epigenetic events in NHBE and particularly sensitive COPD-DHBE cells repeatedly exposed to air pollution-derived PM2.5 and their different responsiveness. While these specific epigenetic changes have been already described in COPD and even lung cancer phenotypes, our findings supported that, together with genetic events, these epigenetic events could dramatically contribute to the shift from healthy to diseased phenotypes following repeated exposure to relatively low doses of air pollution-derived PM2.5. |
| Databáze: | OpenAIRE |
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