Construction and evaluation of drug-metabolizing cell line for bioartificial liver support system.
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.
Omasa
Takeshi
T
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita Osaka 565-0871, Japan. omasa@bio.eng.osaka-u.ac.jp
Kim
Kazumi
K
Hiramatsu
Shinya
S
Katakura
Yoshio
Y
Kishimoto
Michimasa
M
Enosawa
Shin
S
Ohtake
Hisao
H
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004112:Dimercaprol / Q000378:metabolism* / Q000493:pharmacokinetics; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019164:Liver, Artificial; D008657:Metabolic Clearance Rate; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D011994:Recombinant Proteins; D004112:Dimercaprol; D000641:Ammonia; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D005974:Glutamate-Ammonia Ligase