Nickel Oxide Nanoparticles Induced Transcriptomic Alterations in HEPG2 Cells.

Nickel oxide nanoparticles (NiO-NPs) are increasingly used and concerns have been raised on its toxicity. Although a few studies have reported the toxicity of NiO-NPs, a comprehensive understanding of NiO-NPs toxicity in human cells is still lagging. In this study, we integrated transcriptomic approach and genotoxic evidence to depict the mechanism of NiO-NPs toxicity in human hepatocellular carcinoma (HepG2) cells. DNA damage analysis was done using comet assay, which showed 26-fold greater tail moment in HepG2 cells at the highest concentration of 100 mu g/ml. Flow cytometric analysis showed concentration dependent enhancement in intracellular reactive oxygen species (ROS). Real-time PCR analysis of apoptotic (p53, bax, bcl2) and oxidative stress (SOD1) genes showed transcriptional upregulation. Transcriptome analysis using qPCR array showed over expression of mRNA transcripts related to six different cellular pathways. Our data unequivocally suggests that NiO-NPs induces oxidative stress, DNA damage, apoptosis and transcriptome alterations in HepG2 cells.