Nickel Increases Chromosomal Abnormalities by Interfering With the Initiation of DNA Repair Pathways

Abstract

Background: Nickel is a carcinogenic, heavy metal released through industrial activities and via natural resources. It is able to cause DNA damages by reducing the efficiency of DNA repair mechanisms. However, the exact time point at which it is able to interfere with these mechanisms is not yet clearly understood. Methods: To find the most nickel-vulnerable time of repair mechanisms, human dermal fibroblasts (HDF) were treated with three doses of nickel before and after X-irradiation. The induced frequency of chromosomal abnormality was studied using micronucleus assay in binucleated cells. The cytotoxicity of different treatments was established using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The results revealed that nickel treatment had a synergistic effect on inducing Micronucleus frequency only when cells were treated 2 hours before X-irradiation. The X-ray treatment of the cells with 5 and 10 mM nickel had a cytotoxic effect mainly when given 6 hours after the irradiation. Conclusion: The results suggest that nickel can interfere with human DNA repair mechanisms only at the start of the process, while having no significant effect on the human DNA repair mechanisms when activated.