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.

中文翻译：

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原代人肝细胞与肝细胞系：评估其对体外纳米毒理学的适用性。

肝细胞细胞系替代动物模型的使用已受到广泛批评，这主要是由于代谢酶的低表达。这项研究比较了人类原代肝细胞与C3A细胞系，以及它们对一组纳米材料（NM；两种ZnO，两种MWCNT，一种Ag和一种正官能化的TiO 2）的反应。就其对NMs的细胞毒性反应（Ag>未包被的ZnO>被包被的ZnO）而言，该细胞系与原代肝细胞非常相似。在MWCNTs和TiO 2 NMs的存在下不能达到LC 3。所有NMs均显着增加IL-8的产生，而TNF-α和IL-6的水平没有变化。测量白蛋白产生作为肝功能的指标。作者发现白蛋白的水平没有变化，只是在LC₅₀浓度下包被的ZnO NM除外。TEM研究显示，原代肝细胞和C3A细胞的NM吸收均相似。同时，作者证实未经处理的原代细胞中CYP450活性水平较高。这项研究表明，C3A细胞系是研究NM诱导的肝细胞摄取，细胞毒性，促炎性细胞因子产生和白蛋白产生方面反应的良好模型。