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Multicenter Study of Acetaminophen Hepatotoxicity Reveals the Importance of Biological Endpoints in Genomic Analyses.

Authors :
Richard P. Beyer
Rebecca C. Fry
Michael R. Lasarev
Lisa A. McConnachie
Lisiane B. Meira
Valerie S. Palmer
Christine L. Powell
Pamela K. Ross
Theo K. Bammler
Blair U. Bradford
Alex B. Cranson
Michael L. Cunningham
Rickie D. Fannin
Gregory M. Higgins
Patrick Hurban
Robert J. Kayton
Kathleen F. Kerr
Oksana Kosyk
Edward K. Lobenhofer
Stella O. Sieber
Source :
Toxicological Sciences; Sep2007, Vol. 99 Issue 1, p326-326, 1p
Publication Year :
2007

Abstract

Gene expression profiling is a widely used technique with data from the majority of published microarray studies being publicly available. These data are being used for meta-analyses and in silico discovery; however, the comparability of toxicogenomic data generated in multiple laboratories has not been critically evaluated. Using the power of prospective multilaboratory investigations, seven centers individually conducted a common toxicogenomics experiment designed to advance understanding of molecular pathways perturbed in liver by an acute toxic dose of N-acetyl-p-aminophenol (APAP) and to uncover reproducible genomic signatures of APAP-induced toxicity. The nonhepatotoxic APAP isomer N-acetyl-m-aminophenol was used to identify gene expression changes unique to APAP. Our data show that c-Myc is induced by APAP and that c-Myc–centered interactomes are the most significant networks of proteins associated with liver injury. Furthermore, sources of error and data variability among Centers and methods to accommodate this variability were identified by coupling gene expression with extensive toxicological evaluation of the toxic responses. We show that phenotypic anchoring of gene expression data is required for biologically meaningful analysis of toxicogenomic experiments. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10966080
Volume :
99
Issue :
1
Database :
Complementary Index
Journal :
Toxicological Sciences
Publication Type :
Academic Journal
Accession number :
33261314
Full Text :
https://doi.org/10.1093/toxsci/kfm150