Mixture toxicity of the combinations of silver nanoparticles and environmental pollutants

Although toxicity of silver nanoparticles (AgNPs) has been well studied, the mixture toxicity of the combination of AgNPs and other environmental pollutants is still largely unknown. Here, we investigated the mixture toxicity of the combinations of AgNPs and common environmental pollutants such as arsenic (As), cadmium (Cd), and chromium (Cr) on human hepatoma cell line (HepG2) at noncytotoxic concentrations based on analyses of cytotoxicity, genotoxicity, reactive oxygen species (ROS) generation, and modes of cell death. In addition, DNA microarray analysis was performed to understand the cellular responses at a molecular level. AgNPs-As and AgNPs-Cd combinations exhibited synergistic effect on cytotoxicity while AgNPs-Cr showed additive effect. The AgNPs-Cd combination caused much stronger synergism than AgNPs-As combination. Based on cellular and molecular level analyses, the synergistic effect could be explained by overproduction of reactive oxygen species (ROS), which induced DNA damage and consequently apoptotic cell death. On the other hand, the additive effect caused by AgNPs-Cr could be attributed to reduction of the mixture toxicity by precipitation of Cr ions. Taken together, our results clearly demonstrated that the mixture toxicity of AgNPs with As, Cd, or Cr at noncytotoxic concentrations had different toxicity effects. Particularly, toxicogenomic approach using DNA microarray was useful to assess the mechanisms of the mixture toxicity.