TY - JOUR

T1 - An in vitro liver model--assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials

AU - Kermanizadeh, Ali

AU - Gaiser, Birgit K

AU - Hutchison, Gary R

AU - Stone, Vicki

PY - 2012/7/19

Y1 - 2012/7/19

N2 - 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.

AB - 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.

KW - Antioxidants/pharmacology

KW - Cell Culture Techniques

KW - Cell Line, Tumor

KW - Cell Survival/drug effects

KW - DNA Damage

KW - Dose-Response Relationship, Drug

KW - Glutathione/metabolism

KW - Hepatocytes/drug effects

KW - Humans

KW - Interleukin-8/biosynthesis

KW - Models, Biological

KW - Mutagens/toxicity

KW - Nanoparticles/chemistry

KW - Nanotechnology

KW - Oxidative Stress/drug effects

KW - Particle Size

KW - Reactive Oxygen Species/metabolism

KW - Surface Properties

U2 - 10.1186/1743-8977-9-28

DO - 10.1186/1743-8977-9-28

M3 - Article

C2 - 22812506

VL - 9

SP - 28

JO - Particle and fibre toxicology

JF - Particle and fibre toxicology

SN - 1743-8977

ER -