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Karol L. Thompson,¹ Cynthia A. Afshari,^2,3 Rupesh P. Amin,³ Timothy A. Bertram,⁴ Bruce Car,⁵Michael Cunningham,³ Clive Kind,⁶ Jeffrey A. Kramer,⁴ Michael Lawton,⁴ Michael Mirsky,⁴ Jorge M. Naciff,⁷Victor Oreffo,⁶ P. Scott Pine,¹ and Frank D. Sistare¹

¹Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA; ²Amgen, Inc., Thousand Oaks, California, USA; ³National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA; ⁴Pfizer Inc, St. Louis, Missouri, USA, and Groton, Connecticut, USA; ⁵Bristol-Myers Squibb, Wilmington, Delaware, USA; ⁶AstraZeneca Research and Development, Charnwood, Leicestershire, United Kingdom; ⁷The Procter & Gamble Company, Cincinnati, Ohio, USA

Abstract
Within the International Life Sciences Institute Committee on Genomics, a working group was formed to focus on the application of microarray technology to preclinical assessments of drug-induced nephrotoxicity. As part of this effort, Sprague-Dawley rats were treated with the nephrotoxicant cisplatin at doses of 0.3-5 mg/kg over a 4- to 144-hr time course. RNA prepared from these animals was run on a variety of microarray formats at multiple sites. A set of 93 differentially expressed genes associated with cisplatin-induced renal injury was identified on the National Institute of Environmental Health Sciences (NIEHS) custom cDNA microarray platform using quadruplicate measurements of pooled animal RNA. The reproducibility of this profile of statistically significant gene changes on other platforms, in pooled and individual animal replicate samples, and in an independent study was investigated. A good correlation in response between platforms was found among the 48 genes in the NIEHS data set that could be matched to probes on the Affymetrix RGU34A array by UniGene identifier or sequence alignment. Similar results were obtained with genes that could be linked between the NIEHS and Incyte or PHASE-1 arrays. The degree of renal damage induced by cisplatin in individual animals was commensurate with the number of differentially expressed genes in this data set. These results suggest that gene profiles linked to specific types of tissue injury or mechanisms of toxicity and identified in well-performed replicated microarray experiments may be extrapolatable across platform technologies, laboratories, and in-life studies. Key words: cisplatin, cross-platform, kidney, microarrays, nephrotoxicity. Environ Health Perspect 112:488-494 (2004) . doi:10.1289/txg.6676 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 K.L. Thompson, HFD-910, Division of Applied Pharmacology Research, CDER, U.S. FDA, Life Sciences Building 64, 10903 New Hampshire Ave., Silver Spring, MD 20993 USA. Telephone: (301) 796-0126. Fax: (301) 796-9818. E-mail: Thompsonk@cder.fda.gov

We thank and acknowledge J. Collins, J. Miller, J. Chou, and P. Bushel at the National Center for Toxicogenomics, Research Triangle Park, North Carolina, for the BLAST analysis of cDNAs on the NIEHS platform.

The authors declare they have no competing financial interests.

Received 15 August 2003 ; accepted 8 January 2004.

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