Skip Navigation



ToxSci Advance Access published online on November 2, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj033
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
89/2/524    most recent
kfj033v1
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 Volz, D. C.
Right arrow Articles by Kullman, S. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Volz, D. C.
Right arrow Articles by Kullman, S. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 25, 2005
Accepted October 21, 2005

Systems Toxicology

Dynamic Gene Expression Changes Precede Dioxin-Induced Liver Pathogenesis in Medaka Fish

David C. Volz 1, David E. Hinton 1, J. McHugh Law 2, and Seth W. Kullman 1*

1 Integrated Toxicology Program and Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708
2 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606

* To whom correspondence should be addressed.
Seth W. Kullman, E-mail: swkull{at}duke.edu


  Abstract

A major challenge for environmental genomics is linking gene expression to cellular toxicity and morphological alteration. Herein, we address complexities related to hepatic gene expression responses after a single injection of the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and illustrate an initial stress response followed by cytologic and adaptive changes in the teleost fish medaka. Using a custom 175-gene array, we find that overall hepatic gene expression and histological changes are strongly dependent on dose and time. The most pronounced dioxin-induced gene expression changes occurred early and preceded morphologic alteration in the liver. Following a systematic search for putative Ah response elements (AHREs) (5'-CACGCA-3') within 2000 bp upstream of the predicted transcriptional start site, the majority (87%) of genes screened in this study did not contain an AHRE, suggesting that gene expression was not solely dependent on AHRE-mediated transcription. Moreover, in the highest dosage, we observed gene expression changes associated with adaptation that persisted for almost two weeks, including induction of a gene putatively identified as ependymin that may function in hepatic injury repair. These data suggest that the cellular response to dioxin involves both AHRE- and non-AHRE-mediated transcription, and that coupling gene expression profiling with analysis of morphologic pathogenesis is essential for establishing temporal relationships between transcriptional changes, toxicity, and adaptation to hepatic injury.

Keywords: medaka; dioxin; liver; aryl hydrocarbon receptor; gene expression; transcription.
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
D. C. Volz, S. W. Kullman, D. L. Howarth, R. C. Hardman, and D. E. Hinton
Protective Response of the Ah Receptor to ANIT-Induced Biliary Epithelial Cell Toxicity in See-Through Medaka
Toxicol. Sci., April 1, 2008; 102(2): 262 - 277.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H. Wintz, L. J. Yoo, A. Loguinov, Y.-Y. Wu, J. A. Steevens, R. D. Holland, R. D. Beger, E. J. Perkins, O. Hughes, and C. D. Vulpe
Gene Expression Profiles in Fathead Minnow Exposed to 2,4-DNT: Correlation with Toxicity in Mammals
Toxicol. Sci., November 1, 2006; 94(1): 71 - 82.
[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.