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CHIPPING AWAY AT THE MYSTERY OF DRUG RESPONSES
Citation:
Rockett, J C. CHIPPING AWAY AT THE MYSTERY OF DRUG RESPONSES. PHARMACOGENOMICS 1(3):161-163, (2001).
Description:
Chipping away at the mystery of drug responses
John C. Rockett
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Abstract
With many genome projects completed and more soon to follow, focus is beginning to shift from gene discovery to the more complex arena of gene expression and function. In an article recently published in Physiological Genomics by Gerhold et al. (2), the authors confirm what many in the field already ?knew?, or at least strongly suspected - that DNA arrays are indeed useful tools for characterizing gene expression changes induced by drugs, and that these changes are distinct enough to differentiate between drug classes. The study is not terribly unique in that others have already used arrays to detect cytochrome P450 (CYP) genes (3), confirmed gene changes detected by Affymetrix microarrays (4) and conducted proof-of-principle studies on the ability of arrays to discriminate between different drug and chemical responses (5-9). Nevertheless, Gerhold?s experiments were carried out using well-characterized, mechanistically distinct model compounds (3-methylcholanthrene, clofibrate, dexamethasone and phenobarbitol) in a classic exposure model (in vivo rat liver), and the reported findings are well supported by the literature. The genes with altered expression included all the usual suspects (CYPs, glutathione S-transferases, UDP-glucuronyl transferases etc.), and thus provide further evidence for pharmacologists that arrays can indeed ?provide a facile overview of gene expression responses relevant to drug metabolism and toxicology?.