Toxicogenomic responses of human liver HepG2 cells to silver nanoparticles

J Appl Toxicol. 2015 Oct;35(10):1160-8. doi: 10.1002/jat.3170. Epub 2015 May 26.


The increased use of silver nanoparticles (AgNPs) in foods and cosmetics has raised public safety concerns. However, only limited knowledge exists on the effect of AgNPs on the cellular transcriptome. This study evaluated global gene expression profiles of human liver HepG2 cells exposed to 20 and 50 nm AgNPs for 4 and 24 h at 2.5 µg ml(-1) . Exposure to 20 nm AgNPs resulted in 811 altered genes after 4 h, but much less after 24 h. Exposure to 50 nm AgNPs showed minimal altered genes at both exposure times. The HepG2 cells responded to the toxic insult of AgNPs by transiently upregulating stress response genes such as metallothioneins and heat shock proteins. Functional analysis of the altered genes showed more than 20 major biological processes were affected, of which metabolism, development, cell differentiation and cell death were the most dominant categories. Several cellular pathways were also impacted by AgNP exposure, including the p53 signaling pathway and the NRF2-mediated oxidative stress response pathway, which may lead to increased oxidative stress and DNA damage in the cell and potentially result in genotoxicity and carcinogenicity. Together, these results indicate that HepG2 cells underwent a multitude of cellular processes in response to the toxic insult of AgNP exposure, and suggest that toxicogenomic characterization of human HepG2 cells could serve as an alternative model for assessing toxicities of NPs.

Keywords: DNA damage; DNA microarray; HepG2 cells; Silver nanoparticles; alternative model; carcinogenicity; gene expression; genotoxicity; oxidative stress; toxicogenomics.

MeSH terms

  • Cell Differentiation / drug effects
  • Gene Expression / drug effects
  • Heat-Shock Proteins / metabolism
  • Hep G2 Cells
  • Humans
  • Liver / drug effects*
  • Metal Nanoparticles / toxicity*
  • Metallothionein / metabolism
  • Microarray Analysis
  • Mutagens / toxicity*
  • Oxidative Stress / drug effects
  • RNA / biosynthesis
  • RNA / genetics
  • Signal Transduction / drug effects
  • Silver / toxicity*
  • Toxicogenetics


  • Heat-Shock Proteins
  • Mutagens
  • Silver
  • RNA
  • Metallothionein