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Toxicologic Pathology
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Transcriptional Profiling of the Left and Median Liver Lobes of Male F344/N Rats Following Exposure to Acetaminophen

Irwin D. Richard1, Joel S. Parker2, Edward K. Lobenhofer3, Leo T. Burka1, Pamela E. Blackshear4, Molly K. Vallant1, Edward H. Lebetkin1, Diane F. Gerken5 and Gary A. Boorman1

1 Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
2 Constella Group, Inc., Research Triangle Park, North Carolina 27709, USA
3 Paradigm Genetics Inc., Research Triangle Park, North Carolina 27709, USA
4 Integrated Laboratory Systems, Inc., Research Triangle Park, North Carolina 27709, USA
5 Battelle Science and Technology International, Columbus, Ohio 43201, USA

Correspondence: Address correspondence to: Dr. Richard D. Irwin, ETP, NIEHS, P.O. Box 12233, 111 T. W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA; e-mail:irwin{at}niehs.nih.gov

The liver is a common organ for transcriptional profiling because of its role in xenobiotic metabolism and because hepatotoxicity is a common response to chemical exposure. To explore the impact that sampling different lobes may have on transcriptional profiling experiments we have examined and compared gene expression profiles of the left and median lobes of livers from male F344 rats exposed to toxic and nontoxic doses of acetaminophen. Transcript profiling using micorarrays revealed clear differences in the response of the left and median liver lobes of F344 rats to acetaminophen exposure both at low doses as well as doses that caused hepatotoxicity. Differences were found in the total number of differentially expressed genes in the left and median lobes, the number and identity of genes that were differentially expressed uniquely only in the left or median lobe, and in the patterns of gene expression. While it is not possible to generalize these results to compounds other than acetaminophen or other strains of rat, these results highlight the potential impact of sampling differences on the interpretation of gene expression profiles in the liver.

Key Words: Liver • rat • mRNA • differential gene expression • microarray • variation • transcriptome • lobe differences • left lobe • median lobe

Abbreviations: F344, Fischer 344/N • DGE, Differential Gene Expression • NTP, National Toxicology Program • PCA, Principal Components Analysis • SAM, Significance Analysis of Microarrays

Toxicologic Pathology, Vol. 33, No. 1, 111-117 (2005)
DOI: 10.1080/01926230590522257
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