Genotoxicity and mutagenicity of molybdenum(III) and iron(III) and interactions between these microelements

Background: The aim of this study was to examine the effect of iron(III) (Fe(III)) and molybdenum(III) (Mo(III)) and their combinations on genotoxicity, mutagenicity, pro- and antioxidant activity in BALB/3T3 and HepG2 cells. Materials and methods: The cells were cultured in media supplemented with iron chloride or molybdenum trioxide at concentrations of 200 or 1,000 mu M. Moreover, the cells exposed to a mixture of microelements: 200 mu M of iron chloride plus 1,000 mu M of molybdenum trioxide and, in the other case, supplemented with 200 mu M of molybdenum trioxide plus 1,000 mu M of iron chloride. After 24 hours of incubation, comet, micronucleus, and Ames assays were performed. Additionally, DCFDA Cellular ROS Detection Assay, TBARS Assay, SOD Assay, Catalase Assay, and Glutathione Peroxidase Assay were performed. Results: Additions of Fe(III) at 200 mu M plus Mo(III) at 1,000 mu M showed synergistic effect - the increased number of comets and micronuclei in both cell lines was observed. Moreover, the number of revertants increased as well. In the case of Fe(III) at 1,000 AM plus Mo(III) at 200 mu M, the same effect was observed. Moreover, treated cells display characteristic apoptosis in comparison to control cells. Giant and multinuclear cells were observed. In all tested microelements, the increase in number of reverse mutations was observed with and without metabolic activation. The level of reactive oxygen species and malondialdehyde (MDA) in cells increased after simultaneous exposure of cells with 200 mu M iron chloride plus 1,000 mu M molybdenum trioxide. The similar results in the case of interaction of 1,000 mu M of iron chloride plus 200 mu M of molybdenum trioxide were observed. Superoxide dismutase, catalase, and glutathione peroxidase activities decrease in a statistically significant and dose-dependent way after treatment with iron chloride and molybdenum trioxide. Conclusion: Iron and molybdenum are genotoxic and mutagenic. In our study Fe(III) and Mo(III) show synergistic effects in genotoxicity and mutagenicity assays. Both of them can generate ROS. Moreover, Fe(III) interacts with DNA bases. These independent mechanisms can cause synergistic effects.