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

Abstract

Abstract. Background: Nickel and iron are essential and necessary elements required for correct functioning of the human body when found in trace amounts, but their excess can be toxic for cells. They are widely used in numerous industrial applications as components in orthopedic implants and in dietary supplementation. The aim of this study was to examine the effect of nickel(II) and iron(III) and their combinations on genotoxicity and mutagenicity in BALB/3T3 and HepG2 cells. Materials and methods: Genotoxicity of nickel and iron and their mixture was assessed by analyzing induction of ­micronucleus formation and DNA damage by comet assay in BALB/3T3 and HepG2 cells. Mutagenicity of iron(III) and nickel(II) and their mixtures was assessed by Ames assay. Results: A statistically significant increase of DNA damage through use of both microelements in both cell lines was observed. The micronucleus assay performed with the use of all concentrations showed a statistically significant induction of chromosomal aberrations in both tested microelements in both cell lines. The results obtained from both cell lines in both tests show that BALB/3T3 cells are more sensitive when compared to the HepG2 cells after incubation with both microelements. Additions of iron(III) at 200 µM plus nickel(II) at 1,000 µM showed antagonistic effects in a decrease of genotoxicity as assessed by comet and micronuclei assays in both cell lines. In the case of nickel(II) at 200 µM plus iron(III) at 1,000 µM, a synergistic effect was observed. The results of Ames assay show that both tested microelements caused an increased number of reverse mutations. Conclusion: Nickel(II) and iron(III) are genotoxic. Nickel chloride evokes frameshift mutation more often than base-pair substitution mutation. However, in the case of iron chloride, the frequency in frameshift and base-pair substitution mutation was similar. Iron(III) at concentrations of 200 µM plays a protective role against nickel(II) genotoxicity and mutagenicity.