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Identification of Platform-Independent Gene Expression Markers of Cisplatin Nephrotoxicity

By Thompson, Karol L.

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Book Id: WPLBN0000001346
Format Type: PDF eBook
File Size: 0.3 MB
Reproduction Date: 2005

Title: Identification of Platform-Independent Gene Expression Markers of Cisplatin Nephrotoxicity  
Author: Thompson, Karol L.
Language: English
Subject: Government publications, United Nations., United Nations. Office for Disarmament Affairs
Collections: Government Library Collection, Disarmament Documents
Publication Date:
Publisher: United Nations- Office for Disarmament Affairs (Unoda)


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Thompson, K. L. (n.d.). Identification of Platform-Independent Gene Expression Markers of Cisplatin Nephrotoxicity. Retrieved from

Government Reference Publication

Excerpt: 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 druginduced 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 wellperformed 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 [15 January 2004].


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