Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways

BACKGROUND: Poorly soluble cobalt (II, III) oxide particles (Co(3)O(4)P) are believed to induce in vitro cytotoxic effects via a Trojan-horse mechanism. Once internalized into lysosomal and acidic intracellular compartments, Co(3)O(4)P 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 Co(3)O(4)P by performing a comprehensive investigation of the DNA damage exerted in BEAS-2B human bronchial epithelial cells. RESULTS: Our results demonstrate that poorly soluble Co(3)O(4)P enhanced the formation of micronuclei in binucleated cells. Moreover, by comet assay we showed that Co(3)O(4)P induced primary and oxidative DNA damage, and by scoring the formation of γ-H2Ax foci, we demonstrated that Co(3)O(4)P also generated double DNA strand breaks. CONCLUSIONS: By comparing the effects exerted by poorly soluble Co(3)O(4)P with those obtained in the presence of soluble cobalt chloride (CoCl(2)), we demonstrated that the genotoxic effects of Co(3)O(4)P are not simply due to the released Co(2+) but are induced by the particles themselves, as genotoxicity is observed at very low Co(3)O(4)P concentrations.