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Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents

hal.structure.identifierLaboratoire Lésions des Acides Nucléiques [LAN]
dc.contributor.authorARMAND, Lucie
hal.structure.identifierLaboratoire Lésions des Acides Nucléiques [LAN]
dc.contributor.authorTARANTINI, Adeline
hal.structure.identifierLaboratoire Lésions des Acides Nucléiques [LAN]
dc.contributor.authorBÉAL, David
hal.structure.identifierLaboratoire Lésions des Acides Nucléiques [LAN]
dc.contributor.authorBIOLA-CLIER, Mathilde
hal.structure.identifierLaboratoire Lésions des Acides Nucléiques [LAN]
dc.contributor.authorBOBYK, Laure
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorSORIEUL, Sephanie
hal.structure.identifier[GIN] Grenoble Institut des Neurosciences [GIN]
dc.contributor.authorPERNET-GALLAY, Karin
hal.structure.identifierNanoSafety Platform [NPS]
dc.contributor.authorMARIE-DESVERGNE, Caroline
hal.structure.identifierSchool of Geography, Earth and Environmental Sciences [Birmingham]
dc.contributor.authorLYNCH, Iseult
hal.structure.identifierLaboratoire Edifices Nanométriques [LEDNA]
dc.contributor.authorHERLIN-BOIME, Nathalie
hal.structure.identifierLaboratoire Lésions des Acides Nucléiques [LAN]
dc.contributor.authorCARRIÈRE, Marie
dc.date.issued2016-03-16
dc.identifier.issn1743-5390
dc.description.abstractEnAbstractTitanium dioxide nanoparticles (TiO2-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1?50??g/mL TiO2-NPs, 86% anatase/14% rutile, 24?±?6?nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO2-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO2-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO2-NPs.
dc.description.sponsorshipINITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE
dc.language.isoen
dc.publisherTaylor & Francis
dc.title.enLong-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents
dc.typeArticle de revue
dc.identifier.doi10.3109/17435390.2016.1141338
dc.subject.halChimie/Matériaux
dc.subject.halSciences du Vivant [q-bio]
dc.subject.halSciences du Vivant [q-bio]/Biologie cellulaire
dc.subject.halSciences du Vivant [q-bio]/Toxicologie
dc.description.sponsorshipEuropeEngineered nanomaterial mechanisms of interactions with living systems and the environment: a universal framework for safe nanotechnology
dc.description.sponsorshipEuropeA pan-European infrastructure for quality in nanomaterials safety testing
bordeaux.journalNanotoxicology
bordeaux.page913 - 923
bordeaux.volume10
bordeaux.issue7
bordeaux.peerReviewedoui
hal.identifiercea-01651136
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//cea-01651136v1
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