Skip Navigation



ToxSci Advance Access published online on March 31, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh128
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
79/2/411    most recent
kfh128v1
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 Heijne, W. H. M.
Right arrow Articles by van Ommen, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heijne, W. H. M.
Right arrow Articles by van Ommen, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received December 15, 2003; accepted March 2, 2004
© 2004 Toxicological Sciences © Society of Toxicology 2004; all rights reserved.

Systems Toxicology

Bromobenzene-Induced Hepatotoxicity at the Transcriptome Level

Wilbert H. M. Heijne 1*, Angela L. Slitt 2, Peter J. van Bladeren 3, John P. Groten 1, Curtis D. Klaassen 2, Rob H. Stierum 1, and Ben van Ommen 1

1 Department of Biomolecular Sciences, TNO Nutrition and Food Research, PO Box 360, 3700 AJ Zeist, The Netherlands
2 Department of Pharmacology, Toxicology & Therapeutics, University of Kansas, Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 U.S.A.
3 Department of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands

* To whom correspondence should be addressed. E-mail: Heijne{at}voeding.TNO.nl.


  Abstract

Rats were exposed to three levels of bromobenzene, sampled at 6, 24 and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6, but many genes were differentially expressed after 24 h, while after 48 h, only the high dose elicited large effects. Differentially expressed genes were involved in drug metabolism (upregulated GSTs, mEH, NQO1, Mrps, downregulated CYPs, sulfotransferases), oxidative stress (induced HO-1, peroxiredoxin, ferritin), GSH depletion (induced GCS-l, GSTA, GSTM) the acute phase response, and in processes like cholesterol, fatty acid and protein metabolism, and intracellular signaling. Trancriptional regulation via the electrophile and sterol response elements seemed to mediate part of the response to bromobenzene. Recovery of the liver was suggested in response to BB by the altered expression of genes involved in protein synthesis and cytoskeleton rearrangement. Futhermore, after 48 h, rats in the mid dose group showed no toxicity, and gene expression patterns resembled the normal situation. For certain genes (eg. CYP4A, metallothioneins), intraday variation in expression levels was found, regardless of the treatment. Selected cDNA microarray measurements were confirmed using the specific and sensitive branched DNA signal amplification assay.

Key Words: toxicogenomics, bromobenzene, transcriptomics, hepatotoxicity, rat, cDNA microarray .


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
N. Zidek, J. Hellmann, P.-J. Kramer, and P. G. Hewitt
Acute Hepatotoxicity: A Predictive Model Based on Focused Illumina Microarrays
Toxicol. Sci., September 1, 2007; 99(1): 289 - 302.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Tanaka, J. M. Maher, C. Chen, and C. D. Klaassen
Hepatic Ischemia-Reperfusion Induces Renal Heme Oxygenase-1 via NF-E2-Related Factor 2 in Rats and Mice
Mol. Pharmacol., March 1, 2007; 71(3): 817 - 825.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
D. R. Boverhof, L. D. Burgoon, C. Tashiro, B. Sharratt, B. Chittim, J. R. Harkema, D. L. Mendrick, and T. R. Zacharewski
Comparative Toxicogenomic Analysis of the Hepatotoxic Effects of TCDD in Sprague Dawley Rats and C57BL/6 Mice
Toxicol. Sci., December 1, 2006; 94(2): 398 - 416.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
W. H. M. Heijne, R.-J. A. N. Lamers, P. J. van Bladeren, J. P. Groten, J. H. J. van Nesselrooij, and B. van Ommen
Profiles of Metabolites and Gene Expression in Rats with Chemically Induced Hepatic Necrosis
Toxicol Pathol, June 1, 2005; 33(4): 425 - 433.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
L. M. Aleksunes, A. M. Slitt, N. J. Cherrington, M. S. Thibodeau, C. D. Klaassen, and J. E. Manautou
Differential Expression of Mouse Hepatic Transporter Genes in Response to Acetaminophen and Carbon Tetrachloride
Toxicol. Sci., January 1, 2005; 83(1): 44 - 52.
[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.