Omasa Takeshi, Kim Kazumi, Hiramatsu Shinya, Katakura Yoshio, Kishimoto Michimasa, Enosawa Shin, Ohtake Hisao
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita Osaka 565-0871, Japan.
Biotechnol Prog. 2005 Jan-Feb;21(1):161-7. doi: 10.1021/bp049757a.
Focusing on drug metabolism in liver, we constructed and evaluated a drug-metabolizing bioartificial liver (BAL) support system. In a previous study, we constructed ammonia-metabolizing CHO and hepatoma-derived HepG2 cell lines by recombination of the glutamine synthetase (GS) gene. For further mimicking of liver metabolism, the human hepatoma-derived cell line HepG2 was transformed by the pBudCE-GS-CYP3A4 vector, which contains GS and drug-metabolizing CYP 3A4 genes. The constructed GS-3A4-HepG2 cell line showed 3A4 activity higher than that of human primary hepatocytes. The drug-metabolizing activity of BAL (BAL clearance) was evaluated using this cell line. The estimated clearance was higher than that of the human hepatocyte system.
聚焦于肝脏中的药物代谢，我们构建并评估了一种药物代谢生物人工肝（BAL）支持系统。在先前的研究中，我们通过谷氨酰胺合成酶（GS）基因重组构建了氨代谢CHO细胞系和肝癌衍生的HepG2细胞系。为了进一步模拟肝脏代谢，人肝癌衍生细胞系HepG2用包含GS和药物代谢CYP 3A4基因的pBudCE-GS-CYP3A4载体进行转化。构建的GS-3A4-HepG2细胞系显示出比人原代肝细胞更高的3A4活性。使用该细胞系评估了BAL的药物代谢活性（BAL清除率）。估计的清除率高于人肝细胞系统。
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