| Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes. | |
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MedLine Citation:
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PMID: 21149542 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Lei Guo; Stacey Dial; Leming Shi; William Branham; Jie Liu; Jia-Long Fang; Bridgett Green; Helen Deng; Jim Kaput; Baitang Ning |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. Date: 2010-12-13 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 39 ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-18 Completed Date: 2011-06-14 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: United States |
Other Details:
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Languages: eng Pagination: 528-38 Citation Subset: IM |
Affiliation:
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Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Biological Transport Cell Line Cell Line, Tumor Cells, Cultured Drug Evaluation, Preclinical / methods Gene Expression Profiling Gene Expression Regulation, Enzymologic* Hepatocytes / enzymology*, metabolism Humans Membrane Transport Proteins / genetics, metabolism Metabolic Detoxication, Drug Oligonucleotide Array Sequence Analysis Pharmacokinetics* RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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N01-DK-7-0004/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Transport Proteins; 0/RNA, Messenger |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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