Similarities and Differences in the Expression of Drug-Metabolizing Enzymes between Human Hepatic Cell Lines and Primary Human Hepatocytes

• Published in: Drug metabolism and disposition Vol. 39; no. 3; pp. 528 - 538
• Main Authors: Guo, Lei, Dial, Stacey, Shi, Leming, Branham, William, Liu, Jie, Fang, Jia-Long, Green, Bridgett, Deng, Helen, Kaput, Jim, Ning, Baitang
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.03.2011; American Society for Pharmacology and Experimental Therapeutics; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Algorithms; Biological and medical sciences; Biological Transport; Cell Line; Cell Line, Tumor; Cells, Cultured; Drug Evaluation, Preclinical - methods; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Hepatocytes - enzymology; Hepatocytes - metabolism; Humans; Inactivation, Metabolic; Medical sciences; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Pharmacokinetics; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; CV; DMET; P450; THLE; GAPDH; PCR; ACTB; PCA; Human; Cell line; Hepatocyte; Digestive system; Enzyme; Liver; Established cell line; Primary; Drug-metabolizing enzyme; In vitro
• ISSN: 0090-9556; 1521-009X; 1521-009X
• DOI: 10.1124/dmd.110.035873

In addition to primary human hepatocytes, hepatoma cell lines, and transfected nonhepatoma, hepatic cell lines have been used for pharmacological and toxicological studies. However, a systematic evaluation and a general report of the gene expression spectra of drug-metabolizing enzymes and transporters (DMETs) in these in vitro systems are not currently available. To fill this information gap and to provide references for future studies, we systematically characterized the basal gene expression profiles of 251 drug-metabolizing enzymes in untreated primary human hepatocytes from six donors, four commonly used hepatoma cell lines (HepG2, Huh7, SK-Hep-1, and Hep3B), and one transfected human liver epithelial cell line. A large variation in DMET expression spectra was observed between hepatic cell lines and primary hepatocytes, with the complete absence or much lower abundance of certain DMETs in hepatic cell lines. Furthermore, the basal DMET expression spectra of five hepatic cell lines are summarized, providing references for researchers to choose carefully appropriate in vitro models for their studies of drug metabolism and toxicity, especially for studies with drugs in which toxicities are mediated through the formation of reactive metabolites.