title: Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes.
abstract: 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.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Stacey
authors.initials: S
authors.lastname: Dial
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
authors.forename: William
authors.initials: W
authors.lastname: Branham
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Fang
authors.forename: Bridgett
authors.initials: B
authors.lastname: Green
authors.forename: Helen
authors.initials: H
authors.lastname: Deng
authors.forename: Jim
authors.initials: J
authors.lastname: Kaput
authors.forename: Baitang
authors.initials: B
authors.lastname: Ning
mesh_terms: D000465:Algorithms; D001692:Biological Transport; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010599:Pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D026901:Membrane Transport Proteins; D012333:RNA, Messenger