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 -