Skip Navigation


ToxSci Advance Access originally published online on February 20, 2007
Toxicological Sciences 2007 97(1):55-64; doi:10.1093/toxsci/kfm023
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
97/1/55    most recent
kfm023v1
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Thomas, R. S.
Right arrow Articles by Halsey, T. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, R. S.
Right arrow Articles by Halsey, T. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Application of Genomic Biomarkers to Predict Increased Lung Tumor Incidence in 2-Year Rodent Cancer Bioassays

Russell S. Thomas1, Linda Pluta, Longlong Yang and Thomas A. Halsey2

The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709-2137

1 To whom correspondence should be addressed. Fax: (919) 558-1300. E-mail: rthomas{at}thehamner.org.

Received December 23, 2006; accepted February 14, 2007


  Abstract

Rodent cancer bioassays are part of a legacy of safety testing that has not changed significantly over the past 30 years. The bioassays are expensive, time consuming, and use hundreds of animals. Fewer than 1500 chemicals have been tested in a rodent cancer bioassay compared to the thousands of environmental and industrial chemicals that remain untested for carcinogenic activity. In this study, we used existing data generated by the National Toxicology Program (NTP) to identify gene expression biomarkers that can predict results from a rodent cancer bioassay. A set of 13 diverse chemicals was selected from those tested by the NTP. Seven chemicals were positive for increased lung tumor incidence in female B6C3F1 mice and six were negative. Female mice were exposed subchronically to each of the 13 chemicals, and microarray analysis was performed on the lung. Statistical classification analysis using the gene expression profiles identified a set of eight probe sets corresponding to six genes whose expression correctly predicted the increase in lung tumor incidence with 93.9% accuracy. The sensitivity and specificity were 95.2 and 91.8%, respectively. Among the six genes in the predictive signature, most were enzymes involved in endogenous and xenobiotic metabolism, and one gene was a growth factor receptor involved in lung development. The results demonstrate that increases in chemically induced lung tumor incidence in female mice can be predicted using gene biomarkers from a subchronic exposure and may form the basis of a more efficient and economical approach for evaluating the carcinogenic activity of chemicals.

Key Words: genomics; biomarkers; rodent cancer bioassays.

2 Present address: Almac Diagnostics, 801-1 Capitola Drive, Durham, NC 27713.


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
R. J. Kavlock, G. Ankley, J. Blancato, M. Breen, R. Conolly, D. Dix, K. Houck, E. Hubal, R. Judson, J. Rabinowitz, et al.
Computational Toxicology--A State of the Science Mini Review
Toxicol. Sci., May 1, 2008; 103(1): 14 - 27.
[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.