Primary human hepatocytes versus hepatic cell line: assessing their suitability for in vitro nanotoxicology
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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Yn: Nanotoxicology, Cyfrol 7, Rhif 7, 11.2013, t. 1255-71.
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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TY - JOUR
T1 - Primary human hepatocytes versus hepatic cell line
T2 - assessing their suitability for in vitro nanotoxicology
AU - Kermanizadeh, Ali
AU - Gaiser, Birgit K
AU - Ward, Michael B
AU - Stone, Vicki
PY - 2013/11
Y1 - 2013/11
N2 - The use of hepatocyte cell lines as a replacement for animal models have been heavily criticised mainly due to low expression of metabolism enzymes. This study compares primary human hepatocytes with the C3A cell line and with respect to their response to a panel of nanomaterials (NMs; two ZnO, two MWCNTs, one Ag and one positively functionalised TiO₂). The cell line was very comparable with the primary hepatocytes with regards to their cytotoxic response to the NMs (Ag > uncoated ZnO > coated ZnO). The LC₅₀ was not attained in the presence of the MWCNTs and the TiO₂ NMs. All NMs significantly increased IL-8 production, with no change in levels of TNF-α and IL-6. Albumin production was measured as an indicator of hepatic function. The authors found no change in levels of albumin with the exception of the coated ZnO NM at the LC₅₀ concentration. NM uptake was similar for both the primary hepatocytes and C3A cells as investigated by TEM. Meanwhile, the authors confirmed greater levels of CYP450 activity in untreated primary cells. This study demonstrates that the C3A cell line is a good model for investigating NM-induced hepatocyte responses with respect to uptake, cytotoxicity, pro-inflammatory cytokine production and albumin production.
AB - The use of hepatocyte cell lines as a replacement for animal models have been heavily criticised mainly due to low expression of metabolism enzymes. This study compares primary human hepatocytes with the C3A cell line and with respect to their response to a panel of nanomaterials (NMs; two ZnO, two MWCNTs, one Ag and one positively functionalised TiO₂). The cell line was very comparable with the primary hepatocytes with regards to their cytotoxic response to the NMs (Ag > uncoated ZnO > coated ZnO). The LC₅₀ was not attained in the presence of the MWCNTs and the TiO₂ NMs. All NMs significantly increased IL-8 production, with no change in levels of TNF-α and IL-6. Albumin production was measured as an indicator of hepatic function. The authors found no change in levels of albumin with the exception of the coated ZnO NM at the LC₅₀ concentration. NM uptake was similar for both the primary hepatocytes and C3A cells as investigated by TEM. Meanwhile, the authors confirmed greater levels of CYP450 activity in untreated primary cells. This study demonstrates that the C3A cell line is a good model for investigating NM-induced hepatocyte responses with respect to uptake, cytotoxicity, pro-inflammatory cytokine production and albumin production.
KW - Albumins/biosynthesis
KW - Animal Testing Alternatives/methods
KW - Cell Line, Tumor
KW - Cell Survival/drug effects
KW - Cytokines/immunology
KW - Dose-Response Relationship, Drug
KW - Endocytosis
KW - Hepatocytes/cytology
KW - Humans
KW - Lethal Dose 50
KW - Microscopy, Electron, Scanning
KW - Microscopy, Electron, Transmission
KW - Nanoparticles/chemistry
KW - Particle Size
KW - Primary Cell Culture
KW - Surface Properties
KW - Toxicity Tests/methods
U2 - 10.3109/17435390.2012.734341
DO - 10.3109/17435390.2012.734341
M3 - Article
C2 - 23009365
VL - 7
SP - 1255
EP - 1271
JO - Nanotoxicology
JF - Nanotoxicology
SN - 1743-5390
IS - 7
ER -