Analyses of transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models

For assessing the cancer-causing potential for humans of a chemical compound, the conventional approach is the use of the 2-year rodent carcinogenicity bioassay, thus alternatives such as in vitro toxicogenomics are highly desired. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically-stabilized cultures of primary rat hepatocytes, the human hepatoma-derived HepaRG and HepG2 cell lines and the human embryonic stem cell-derived hepatocyte-like cells hES-Heps are examined and compared.为评估化学化合物对人类的致癌潜能，常规方法采用两年啮齿类动物致癌性生物试验（2-year rodent carcinogenicity bioassay），因此亟需体外毒理基因组学（in vitro toxicogenomics）等替代方案。本研究针对五种基于肝脏的体外模型，检测并比较了暴露于遗传毒性（genotoxic, GTX）、非遗传毒性（non-genotoxic, NGTX）肝致癌物以及非致癌物（non-carcinogens, NC）后的转录组响应。这五种模型分别为：原代大鼠肝细胞的常规培养体系、表观遗传稳定的原代大鼠肝细胞培养体系、人肝癌来源的HepaRG细胞系、人肝癌来源的HepG2细胞系，以及人胚胎干细胞来源的肝细胞样细胞hES-Heps。