title: Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels.
abstract: To date, in vitro studies assessing the pulmonary toxicity of inhaled particles have provided poor correlation with in vivo results. We explored whether this discrepancy reflected cellular adaptations in pulmonary cells cultured under atmospheric oxygen concentrations (21%) compared with in vivo alveolar concentrations (100 mm Hg, ~ 13%) and whether this blunted cellular responses to nanoparticle challenge. At 21% oxygen, A549 cells had augmented intracellular glutathione concentrations, with evidence of increased tolerance to CuO nanoparticles, with reduced reactive oxygen species production, blunted transcriptional responses and delayed cell death, compared to cells cultured at 13% oxygen. These data support the contention that standard cell culture conditions pre-adapt cells to oxidative insults and emphasize the necessity of ensuring normoxic conditions in model systems to improve their predictive value.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, UK.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Institute of Pharmaceutical Science, King's College London, UK.
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Dailey
authors.affiliation: Institute of Pharmaceutical Science, King's College London, UK.
authors.forename: Magda
authors.initials: M
authors.lastname: Swedrowska
authors.affiliation: Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Siow
authors.affiliation: Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, UK.
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.affiliation: Centre for Ultrastructural Imaging, King's College London, UK.
authors.forename: Gema
authors.initials: G
authors.lastname: Vizcay-Barrena
authors.affiliation: Genomics Centre, King's College London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Arno
authors.affiliation: MRC-PHE Centre for Environment and Health, King's College London, UK.|NIHR Health Protection Research Unit on Environmental Hazards at King's College London in Partnership with Public Health England, London, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Mudway
authors.affiliation: Institute of Pharmaceutical Science, King's College London, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
mesh_terms: D016477:Artifacts; D002460:Cell Line; D003300:Copper / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D017382:Reactive Oxygen Species; D003300:Copper; D005978:Glutathione; D010100:Oxygen; C030973:cupric oxide
keywords: dose; lung; nanoparticle; normoxia; oxidative stress; oxygen