Use of Reporter Genes to Measure Xenobiotic-Mediated Activation of CYP Gene Transcription

Abstract

Transcriptional activation of CYP gene expression by xenobiotics may have fundamental effects on body physiology. It may result in the altered pharmacokinetics of other chemicals in the body, both xenobiotic and endogenous substrates, potentially altering their effects. This may often result in no observable clinical effect, but in a significant number of cases these interactions lead to altered physiology or failure of a therapeutic drug. It is therefore important to be able to screen novel chemical entities for their ability to activate CYP gene expression. In addition, through mechanistic studies of how such transcriptional activation occurs, the ability to predict and avoid such potential interactions is improved. Reporter gene assays provide a simple, high-throughput methodology for examining the transcriptional activation of CYP gene expression by xenobiotics. They are suitable for use in screening as well as mechanistic studies and are of use in both the drug discovery/development and research arenas.