Skip Navigation



ToxSci Advance Access published online on November 17, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl171
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
96/1/40    most recent
kfl171v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Thomas, R. S.
Right arrow Articles by Page, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, R. S.
Right arrow Articles by Page, T. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 25, 2006
Accepted November 14, 2006

Carcinogenicity

A Comparison of Transcriptomic and Metabonomic Technologies for Identifying Biomarkers Predictive of Two-Year Rodent Cancer Bioassays

Russell S. Thomas 1 *, Thomas M. O'Connell 2, Linda Pluta 1, Russell D. Wolfinger 3, Longlong Yang 1, and Todd J. Page 1

1 CIIT Centers for Health Research, 6 Davis Drive, Research Triangle Park, NC 27709-2137
2 Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599
3 SAS Institute Inc., 100 SAS Campus Drive, Cary, NC 27513-2414

* To whom correspondence should be addressed.
Russell S. Thomas, E-mail: rthomas{at}ciit.org


  Abstract

Two-year rodent bioassays play a central role in evaluating the carcinogenic potential of both commercial products and environmental contaminants. The bioassays are expensive and time-consuming, requiring years to complete and costing $2 to $4 million. In this study, we compare transcriptomic and metabonomic technologies for discovering biomarkers that can efficiently and economically identify chemical carcinogens without performing a standard two-year rodent bioassay. Animals were exposed subchronically to two chemicals (one genotoxic and one nongenotoxic) that were positive for lung and liver tumors in a standard two-year bioassay, two chemicals that were negative, and two control groups. Microarray analysis performed on liver and lung tissues identified multiple biomarkers in each tissue that could discriminate between carcinogenic and noncarcinogenic treatments. The discriminating biomarkers shared a common expression profile among carcinogenic treatments despite different genotoxicity categories and potential modes-of-action, suggesting that they reflect underlying cellular changes in the transition towards neoplasia. Statistical classification analysis exhibited 100% accuracy in both tissues when the number of genes was less than 5,000. Additional genes reduced the predictive accuracy of the model. Serum samples were analyzed by 1H NMR and chemical-specific metabolites were removed from the spectra. The statistical classification analysis of the endogenous serum metabolites showed relatively low predictive accuracy with few metabolites in the model, but the accuracy increased to a maximum of 94% when all metabolites were added. These results suggest that individual endogenous metabolites are relatively poor biomarkers, but the metabolite profile as a whole is altered following carcinogen treatment.

Keywords: genomics; metabonomics; biomarkers; rodent cancer bioassays.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
S. Nesnow, W. Ward, T. Moore, H. Ren, and S. D. Hester
Discrimination of Tumorigenic Triazole Conazoles from Phenobarbital by Transcriptional Analyses of Mouse Liver Gene Expression
Toxicol. Sci., July 1, 2009; 110(1): 68 - 83.
[Abstract] [Full Text] [PDF]

Home page
 Schizophr BullHome page
G. I. Elmer and N. Kafkafi
Drug Discovery in Psychiatric Illness: Mining for Gold
Schizophr Bull, March 18, 2009; (2009) sbn194v1.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.