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Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells

hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorORTEGA, Richard
hal.structure.identifierLaboratoire de Spéciation des Radionucléides et des Molécules [LSRM]
dc.contributor.authorBRESSON, Carole
hal.structure.identifierLaboratoire de Biochimie des Systèmes Perturbés [LBSP]
dc.contributor.authorDAROLLES, Carine
hal.structure.identifierLaboratoire d’analyse en soutien aux exploitants [LASE]
dc.contributor.authorGAUTIER, Celine
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorROUDEAU, Stéphane
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorPERRIN, Laura
hal.structure.identifierLaboratoire de développement Analytique Nucléaire Isotopique et Elémentaire [LANIE]
hal.structure.identifierLaboratoire de Géochimie Isotopique Environnementale (GIS) / Université de Nîmes [GIS]
dc.contributor.authorJANIN, Myriam
hal.structure.identifierLaboratoire d'écotoxicologie des radionucléides [IRSN/PRP-ENV/SERIS/LECO]
dc.contributor.authorFLORIANI, Magali
hal.structure.identifierLaboratoire de Biochimie des Systèmes Perturbés [LBSP]
dc.contributor.authorALOIN, Valérie
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorCARMONA, Asuncion
hal.structure.identifierLaboratoire de Biochimie des Systèmes Perturbés [LBSP]
dc.contributor.authorMALARD, Veronique
dc.date.issued2014
dc.identifier.issn1743-8977
dc.description.abstractEnBackground: The mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co 3 O 4).Methods: This study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry.Results: Our study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity.Conclusions: Cobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity.
dc.language.isoen
dc.publisherBioMed Central
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.subject.enToxicity
dc.subject.enLung cells
dc.subject.enCobalt oxide
dc.subject.enParticles
dc.subject.enEndocytosis
dc.subject.enLysosome
dc.subject.enIntracellular solubilization
dc.subject.enPIXE
dc.subject.enICP-MS
dc.title.enLow-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells
dc.typeArticle de revue
dc.identifier.doi10.1186/1743-8977-11-14
dc.subject.halSciences du Vivant [q-bio]/Toxicologie
bordeaux.journalParticle and Fibre Toxicology
bordeaux.page14
bordeaux.volume11
bordeaux.issue1
bordeaux.peerReviewedoui
hal.identifierhal-02899990
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-02899990v1
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