Skip Navigation


ToxSci Advance Access originally published online on June 27, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
75/1/208    most recent
kfg172v1
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 (15)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Jessen, B. A.
Right arrow Articles by Stevens, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jessen, B. A.
Right arrow Articles by Stevens, G. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 75, 208-222 (2003)
Copyright © 2003 by the Society of Toxicology

SYSTEMS TOXICOLOGY

Assessment of Hepatocytes and Liver Slices as in Vitro Test Systems to Predict in Vivo Gene Expression

Bart A. Jessen*,1,2, Jennifer S. Mullins{dagger},1, Ann de Peyster{dagger} and Gregory J. Stevens*

* Pfizer Global Research and Development, 10724 Science Center Drive, La Jolla, California, 92121, and {dagger} Graduate School of Public Health, San Diego State University, San Diego, California 92182

The use of in vitro systems to predict in vivo responses to chemical agents provides the benefits of requiring fewer animals, reducing variability between samples, requiring less test material, and enabling higher throughput. In the present study rat tissue slices and primary hepatocytes were compared as in vitro systems to predict in vivo changes in gene expression in response to treatment with known liver toxicants or inducers. Five compounds (phenobarbital, carbon tetrachloride, Wy-14,634, alpha-napthylisothiocyanate, and tacrine) were chosen for their established and diverse mechanisms of hepatoxicity or microsomal induction. Expression profiles from male Sprague-Dawley rats or in vitro systems treated for 24 h were measured by DNA oligonucleotide microarrays containing 8700 probe sets. Qualitative comparison of expression revealed a >80% concordance between in vivo liver and both in vitro systems; however, the responsiveness of both in vitro systems to compound-induced changes in gene expression was far less than that of in vivo. Furthermore, both in vitro systems appeared similar in their ability to reproduce compound-induced changes in gene expression observed in vivo.

Key Words: microarray; hepatocytes; liver slices; hepatotoxicity; gene expression.


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
Y. Zhou, V. S. Vaidya, R. P. Brown, J. Zhang, B. A. Rosenzweig, K. L. Thompson, T. J. Miller, J. V. Bonventre, and P. L. Goering
Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium
Toxicol. Sci., January 1, 2008; 101(1): 159 - 170.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. T. Rein, M. Breidenbach, T. O. Kirby, T. Han, G. P. Siegal, G. J. Bauerschmitz, M. Wang, D. M. Nettelbeck, Y. Tsuruta, M. Yamamoto, et al.
A Fiber-Modified, Secretory Leukoprotease Inhibitor Promoter-Based Conditionally Replicating Adenovirus for Treatment of Ovarian Cancer
Clin. Cancer Res., February 1, 2005; 11(3): 1327 - 1335.
[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.