An in vitro liver model--assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials.
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 implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five titanium dioxide (TiO2), two zinc oxide (ZnO), two multi-walled carbon nanotubes (MWCNT) and one silver (Ag) NM) on oxidative responses of C3A cell line as a model for potential detrimental properties of nanomaterials on the liver.


RESULTS
We noted a dose dependant decrease in the cellular glutathione content following exposure of the C3A cells to Ag, the ZnO and the MWCNTs. Intracellular ROS levels were also measured and shown to increase significantly following exposure of the C3A to the low toxicity NMs (MWCNT and TiO(2)). The antioxidant Trolox in part prevented the detrimental effect of NMs on cell viability, and decreased the NM induced IL8 production after exposure to all but the Ag particulate. Following 4 hr exposure of the C3A cells to sub-lethal levels of the NMs, the largest amount of DNA damage was induced by two of the TiO(2) samples (7 nm and the positively charged 10 nm particles).


CONCLUSIONS
All ten NMs exhibited effects on the hepatocyte cell line that were at least in part ROS/oxidative stress mediated. These effects included mild genotoxicity and IL8 production for all NM except the Ag possibly due to its highly cytotoxic nature.
Heriot-Watt University, School of Life Sciences, Nanosafety Research Group, Edinburgh, EH14 4AS, UK. ak435@hw.ac.uk
Ali
A
Kermanizadeh
Birgit K
BK
Gaiser
Gary R
GR
Hutchison
Vicki
V
Stone
D000975:Antioxidants / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D036103:Nanotechnology; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties
D000975:Antioxidants; D016209:Interleukin-8; D009153:Mutagens; D017382:Reactive Oxygen Species; D005978:Glutathione