An in vitro liver model--assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials
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In: Particle and fibre toxicology, Vol. 9, 19.07.2012, p. 28.
Research output: Contribution to journal › Article › peer-review
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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 -