In vitro genotoxic effects of different combinations of cobalt and metallic carbide particles.

De Boeck, Marlies Lombaert, Noömi De Backer, Sofie Finsy, Robert Lison, Dominique [UCL] Kirsch-Volders, Micheline

Occupational exposure to hard metal dust, consisting of tungsten carbide (WC) and metallic cobalt particles (Co), is associated with an increased risk of lung cancer, while no increased risk was observed in workers exposed to Co alone. In vitro, in human peripheral blood mononucleated cells (PBMC), we previously demonstrated that WC-Co is more genotoxic than Co and WC alone. A possible mechanism underlying this higher genotoxicity is a specific physicochemical interaction between Co and WC particles leading to the enhanced short-term formation of active oxygen species. The aim of this study was to evaluate the in vitro genotoxicity of other combinations of Co with metal carbide particles in comparison with WC-Co. The ability of Cr(3)C(2), Mo(2)C and NbC and of their powder mixtures with Co to induce DNA strand breaks and alkali-labile sites was assessed by the alkaline Comet assay and their potential to induce chromosome(/genome) mutations by the cytokinesis-block micronucleus test on human PBMC from two donors. PBMC were treated in vitro for 15 min, 24 h after the onset of PHA stimulation. In the micronucleus test, while the metal carbides alone did not increase the micronucleus frequency, Co alone and the four tested carbide-Co mixtures induced a statistically significant concentration-dependent increase in micronucleated binucleates. In addition to WC, NbC and Cr(3)C(2) particles were able to interact with Co, producing a higher mutagenic effect than the individual metal particles. Mo(2)C particles did not display interactive mutagenicity with Co in the micronucleus test, possibly related to their small specific surface area, compactness and/or spherical shape. With the Comet assay, applied directly at the end of the treatment, less clear results, due to inter-experimental and inter-donor variation, were obtained. These data indicate that particular interaction of a metal carbide with Co leading to enhanced mutagenicity is not specific for WC.