title: Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways.
abstract: BACKGROUND
  Poorly soluble cobalt (II, III) oxide particles (Co3O4P) are believed to induce in vitro cytotoxic effects via a Trojan-horse mechanism. Once internalized into lysosomal and acidic intracellular compartments, Co3O4P slowly release a low amount of cobalt ions (Co(2+)) that impair the viability of in vitro cultures. In this study, we focused on the genotoxic potential of Co3O4P by performing a comprehensive investigation of the DNA damage exerted in BEAS-2B human bronchial epithelial cells.
  
  
  RESULTS
  Our results demonstrate that poorly soluble Co3O4P enhanced the formation of micronuclei in binucleated cells. Moreover, by comet assay we showed that Co3O4P induced primary and oxidative DNA damage, and by scoring the formation of γ-H2Ax foci, we demonstrated that Co3O4P also generated double DNA strand breaks.
  
  
  CONCLUSIONS
  By comparing the effects exerted by poorly soluble Co3O4P with those obtained in the presence of soluble cobalt chloride (CoCl2), we demonstrated that the genotoxic effects of Co3O4P are not simply due to the released Co(2+) but are induced by the particles themselves, as genotoxicity is observed at very low Co3O4P concentrations.
authors: Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Aix Marseille Université, CNRS, IRD, Avignon Université, Equipe Biogénotoxicologie, Santé Humaine et Environnement, Faculté de Médecine Timone, Marseille, France.
authors: Chiara
authors: C
authors: Uboldi
authors: Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Aix Marseille Université, CNRS, IRD, Avignon Université, Equipe Biogénotoxicologie, Santé Humaine et Environnement, Faculté de Médecine Timone, Marseille, France.
authors: Thierry
authors: T
authors: Orsière
authors: CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), Perturbed Systems Biochemistry Laboratory (LBSP), Bagnols-sur-Cèze, France.
authors: Carine
authors: C
authors: Darolles
authors: CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), Perturbed Systems Biochemistry Laboratory (LBSP), Bagnols-sur-Cèze, France.
authors: Valérie
authors: V
authors: Aloin
authors: Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Aix Marseille Université, CNRS, IRD, Avignon Université, Equipe Biogénotoxicologie, Santé Humaine et Environnement, Faculté de Médecine Timone, Marseille, France.
authors: Virginie
authors: V
authors: Tassistro
authors: CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), Perturbed Systems Biochemistry Laboratory (LBSP), Bagnols-sur-Cèze, France.|CEA, DSV, Institute of Biology and Technology Saclay (Ibitec-s), Molecular Labeling and Bio-organic Chemistry Unit (SCBM), Gif sur Yvette, France.
authors: Isabelle
authors: I
authors: George
authors: CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), Perturbed Systems Biochemistry Laboratory (LBSP), Bagnols-sur-Cèze, France. veronique.malard@cea.fr.|CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), IBEB, Laboratoire des Interactions Protéine Métal, Saint-Paul-Lez-Durance, France. veronique.malard@cea.fr.
authors: Véronique
authors: V
authors: Malard
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D053903:DNA Breaks, Double-Stranded; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006657:Histones / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure; D053768:Metal Nanoparticles; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D018570:Risk Assessment; D012995:Solubility
chemical_list: C468783:H2AX protein, human; D006657:Histones; D010087:Oxides; D003035:Cobalt; C018021:cobaltous chloride; C060728:cobalt oxide