An in vitro liver model - assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials

ABSTRACT: BACKGROUND: Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials(NM) have been shown to translocate to the liver. Since oxidative stress has been implicatedas a possible mechanism for NM toxicity this study aimed to investigate the effects of variousmaterials (five titanium dioxide (TiO2), two zinc oxide (ZnO), two multi-walled carbonnanotubes (MWCNT) and one silver (Ag) NM) on oxidative responses of C3A cell line as amodel for potential detrimental properties of nanomaterials on the liver. RESULTS: We noted a dose dependant decrease in the cellular glutathione content following exposure ofthe C3A cells to Ag, the ZnO and the MWCNTs. Intracellular ROS levels were alsomeasured and shown to increase significantly following exposure of the C3A to the lowtoxicity NMs (MWCNT and TiO2). The antioxidant Trolox in part prevented the detrimentaleffect of NMs on cell viability, and decreased the NM induced IL8 production after exposureto all but the Ag particulate. Following 4 hr exposure of the C3A cells to sub-lethal levels ofthe NMs, the largest amount of DNA damage was induced by two of the TiO2 samples (7 nmand the positively charged 10 nm particles). CONCLUSIONS: All ten NMs exhibited effects on the hepatocyte cell line that were at least in partROS/oxidative stress mediated. These effects included mild genotoxicity and IL8 productionfor all NM except the Ag possibly due to its highly cytotoxic nature.