title: Systematic and simultaneous gene profiling of 84 drug-metabolizing genes in primary human hepatocytes.
abstract: Drug-metabolizing enzymes are an important battery of proteins that are involved in drug metabolism, xenobiotic detoxification, and drug-induced toxicity. Systematic, efficient, and simultaneous evaluation of drug-metabolizing gene expression in response to chemicals has a wide variety of implications in drug development, disease prevention, and personalized medicine and nutrition. In the current study, the authors have systematically and simultaneously evaluated the hepatic expression profile of drug-metabolizing enzymes in cultured human hepatocytes exposed to the xenobiotics rifampicin, omeprazole, and 3-methylcholanthrene (3-MC) using the Drug Metabolism RT(2)Profiler PCR Arrays. This new high-throughput tool allowed the authors to evaluate the expression of genes coding for 84 drug-metabolizing enzymes (including phase 1 and phase 2 drug-metabolizing enzymes and transporters) simultaneously, in a 96-well format using a small amount of experimental materials. To validate the quality of the Drug Metabolism RT(2)Profiler PCR Arrays, the PCR Array was compared with the well-documented platform TaqMan assay, and a high concordance was shown between these 2 methods, indicating the high reliability of the Drug Metabolism RT(2)Profiler PCR Arrays. In addition, increasing or decreasing the expression of drug-metabolizing enzymes by these 3 compounds was observed, and underlying mechanisms are discussed.
authors.affiliation: Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas 72079, USA.
authors.forename: Baitang
authors.initials: B
authors.lastname: Ning
authors.forename: Stacey
authors.initials: S
authors.lastname: Dial
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Jingping
authors.initials: J
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
mesh_terms: D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008748:Methylcholanthrene / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D012313:RNA / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology
chemical_list: D008748:Methylcholanthrene; D012313:RNA; D009853:Omeprazole; D012293:Rifampin