The Utility of DNA Microarrays for Characterizing Genotoxicity Ronald K. Newton,1 Marilyn Aardema,2 and Jiri Aubrecht3 1Division of Toxicology, Lilly Research Laboratories, Eli Lilly
and Company, Greenfield, Indiana, USA; 2Miami Valley Laboratories,
The Procter & Gamble Company, Cincinnati, Ohio, USA; 3Global
Research and Development, Pfizer Inc, Groton, Connecticut, USA Abstract Microarrays provide an unprecedented opportunity for comprehensive concurrent analysis of thousands of genes. The global analysis of the response of genes to a toxic insult (toxicogenomics) , as opposed to the historical method of examining a few select genes, provides a more complete picture of toxicologically significant events. Here we examine the utility of microarrays for providing mechanistic insights into the response of cells to DNA damage. Our data indicate that the value of the technology is in its potential to provide mechanistic insight into the mode of action of a genotoxic compound. Array-based expression profiling may be useful for differentiating compounds that interact directly with DNA from those compounds that are genotoxic via a secondary mechanism. As such, genomic microarrays may serve as a valuable alternative methodology that helps discriminate between these two classes of compounds. Key words: biomarkers, gene expression profile, genetic toxicology, mechanism of action, toxicogenomics. Environ Health Perspect 112:420-422 (2004) . doi:10.1289/txg.6709 available via http://dx.doi.org/ [Online 15 January 2004] This article is part of the mini-monograph "Application of Genomics to Mechanism-Based Risk Assessment." Address correspondence to J. Aubrecht, Pfizer Inc, Global Research and Development, Eastern Point Rd., Groton, CT 06355. Telephone: (860) 715-3384. Fax: (860) 715-7884. E-mail: jiri_aubrecht@groton.pfizer.com We thank members of the HESI Genomics Steering Committee for comments and review of the manuscript. The authors declare they have no competing financial interests. Received 28 August 2003 ; accepted 3 December 2003. The full version of this article is available for free in HTML or PDF formats. |