Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways
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RESEARCH
Open Access
Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways Chiara Uboldi1, Thierry Orsière1, Carine Darolles2, Valérie Aloin2, Virginie Tassistro1, Isabelle George2,3 and Véronique Malard2,4*
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 (Co2+) 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 Co2+ but are induced by the particles themselves, as genotoxicity is observed at very low Co3O4P concentrations. Keywords: Cobalt oxide nanoparticles, Human lung cells, Cytotoxicity, Genotoxicity, micronuclei, Comet assay, Foci formation, Oxidative stress
Background The industrial application of cobalt nanoparticles ranges from supercapacitors [1, 2] and pseudocapacitors [3, 4] to sensors [5, 6], while in biomedicine they are mainly employed in magnetic resonance imaging [7] and as nonviral DNA carriers in gene therapy [8–10]. Although the use of cobalt particles has improved many industrial and biomedical applications, their biocompatibility and permanence in tissues and cells remains an open issue. Human occupational exposure to cobalt particles can be accidental [11, 12] or chronic, and the main route of exposure is inhalation during the production of the particles themselves or of the nanobased products. When dispersed in aqueous solutions, cobalt nanoparticles undergo leaching and release cobalt ions (Co2+). This * Correspondence: [email protected] 2 CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), Perturbed Systems Biochemistry Laboratory (LBSP), Bagnols-sur-Cèze, France 4 CEA, DSV, Institute of Environmental Biology and Biotechnology (IBEB), IBEB, Laboratoire des Interactions Protéine Métal, Saint-Paul-Lez-Durance, France Full list of author information is available at the end of the article
peculiarity has been shown to depend on their chemical form: metallic cobalt and cobalt (II) oxide particles (CoOP) are significantly more soluble than the cobalt (II, III) oxide, Co3O4P [13, 14]. Nevertheless, while Papis et al. showed that the dissolution of nanosized Co3O4P in cell culture medium is negligibl
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