Enhanced Cytotoxic and Genotoxic Effect of Gadolinium under the ELF-EMF irradiation in Human Lymphocytes

Abstract

Gadolinium (Gd) is widely used for various industrial and medical purposes, particularly in magnetic resonance imaging (MRI) contrast agent. As there has been a large volume of studies about cyto- and geno- toxicity of Gd, it has been utilized as derivatives by chelation with various ligands. Human exposure to Gd and its derivatives is significantly increasing, posing a high risk of accumulation and retention. It is important to investigate the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on the cyto- and geno-toxicity of Gd, since patients are co-exposed to Gd and ELF-EMF generated by MRI scanner. The aim of this study is to investigate the cyto- and geno-toixcity of Gd and the possible enhancing effect of ELF-EMF on the toxicity of Gd in cultured human peripheral blood lymphocytes by performing micronuclei (MN) assay, single cell gel electrophoresis (Comet) assay, trypan blue dye-exclusion assay, apoptosis analysis using flow cytometry and intracellular reactive oxygen species measurement. MN frequencies were 13.0, 14.0, 15.3 and 17.7 per 1000 cells in Gd treatment cells at concentrations of 0, 0.4, 0.8 and 1.2 mM. ELF-EMF exposure (0.8 mT) increased the frequencies of MN induced by Gd treatment alone; 13.3, 17.0, 20.3 and 25.0 per 1000 cells at each Gd concentrations. ELF-EMF exposure also increased cell death, olive tail moment (OTM), apoptosis and ROS level induced by Gd treatment alone. These results suggest that Gd induces DNA damage, apoptotic cell death and ROS generation in human lymphocytes and ELF-EMF can enhance the cyto- and geno-toxicity of Gd.