Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways

Chiara Uboldi (1) , Thierry Orsiere , Carine Darolles , Valérie Aloin (2) , Virginie Tassistro (1) , Isabelle George (3) , Veronique Malard (4, 5)

1 IMBE - Institut méditerranéen de biodiversité et d'écologie marine et continentale
2 LBSP - Laboratoire de Biochimie des Systèmes Perturbés
3 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
4 BIAM - Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB)
5 IPM - Interactions Protéine Métal

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.

Mots clés: Cobalt oxide nanoparticles; Human lung cells; Cytotoxicity; Genotoxicity; micronuclei; Comet assay; Foci formation; Oxidative stress

Domaines: Biodiversité et Ecologie

Chiara Uboldi, Thierry Orsiere, Carine Darolles, Valérie Aloin, Virginie Tassistro, et al.. Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways. Particle and Fibre Toxicology, 2016, 13, ⟨10.1186/s12989-016-0118-8⟩. ⟨hal-01473128⟩