ABSTRACT
Oligonucleotide DNA microarrays were evaluated for measuring classical and nonclassical genomic responses to prototypical cytochrome P450 inducers by monitoring global expression profiles of drug metabolism genes in rat liver. The messenger RNA responses were measured using a Merck Drug Safety Chip employing the 25-mer oligodeoxynucleotide microarray technology from Affymetrix, Inc. Nuclear receptors that regulate drug-metabolizing genes include the pregnane X receptor, the constitutive androstane receptor, the glucocorticoid receptor, the peroxisome proliferator activated receptor alpha, the liver X receptor, and the Farnesoid X-activated receptor. Such a dynamic transcriptional regulatory system provides an opportunity for study by microarray analysis. Although many examples of drug metabolism genes are known to be regulated directly by a nuclear receptor, microarray analyses are beginning to reveal a global picture of how the liver responds to xenobiotics. DNA microarray assays can also be used to compare transcriptional changes caused by drugs or other xenobiotics to elucidate mechanisms of adverse events.
