Construction and Evaluation of Drug-Metabolizing Cell Line for Bioartificial Liver Support System

摘要

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.