Systematic and Simultaneous Gene Profiling of 84 Drug-Metabolizing Genes in Primary Human Hepatocytes

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 RT2Profiler™ 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 RT2Profiler™ 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 RT2Profiler™ PCR Arrays. In addition, increasing or decreasing the expression of drug-metabolizing enzymes by these 3 compounds was observed, and underlying mechanisms are discussed.