Skip Navigation



ToxSci Advance Access published online on September 28, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi341
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
90/1/61    most recent
kfi341v1
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 Tilton, S. C.
Right arrow Articles by Williams, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tilton, S. C.
Right arrow Articles by Williams, D. E.
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 5, 2005
Accepted September 19, 2005

Carcinogenicity

Toxicogenomic Profiling of the Hepatic Tumor Promoters Indole-3-Carbinol, 17{beta}-estradiol and {beta}-naphthoflavone in Rainbow Trout

Susan C. Tilton 1, Scott A. Givan 2, Cliff B. Pereira 3, George S. Bailey 4, and David E. Williams 4*

1 Department of Environmental and Molecular Toxicology, Marine and Freshwater Biomedical Sciences Center and Linus Pauling Institute, Oregon State University, Corvallis, Oregon, 97331
2 Center for Gene Research and Biotechnology, Oregon State University, Corvallis, Oregon, 97331
3 Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon, 97331; Department of Statistics, Oregon State University, Corvallis, Oregon, 97331
4 Department of Environmental and Molecular Toxicology, Marine and Freshwater Biomedical Sciences Center and Linus Pauling Institute, Oregon State University, Corvallis, Oregon, 97331; Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon, 97331

* To whom correspondence should be addressed.
David E. Williams, E-mail: david.williams{at}oregonstate.edu


  Abstract

Indole-3-carbinol (I3C), from cruciferous vegetables, has been found to suppress or enhance tumors in several animal models. We previously reported that dietary I3C promotes hepatocarcinogenesis in rainbow trout (Oncorhynchus mykiss) at concentrations that differentially activated estrogen receptor (ER) or aryl hydrocarbon receptor (AhR)-mediated responses based on individual protein biomarkers. In this study, we evaluated the relative importance of these pathways as potential mechanisms for I3C on a global scale. Hepatic gene expression profiles were examined in trout after dietary exposure to 500 and 1500 ppm I3C and 3,3,-diindolylmethane (DIM), a major in vivo component of I3C, and were compared to the transcriptional signatures of two model hepatic tumor promoters; 17{beta}-estradiol (E2), an ER agonist, and {beta}-naphthoflavone, an AhR agonist. We demonstrate that I3C and DIM acted similar to E2 at the transcriptional level based on correlation analysis of expression profiles and clustering of gene responses. Of the genes regulated by E2 (fold change ≥2.0 or ≤0.50), most genes were regulated similarly by DIM (87-92%) and I3C (71%) suggesting a common mechanism of action. Of interest were upregulated genes associated with signaling pathways for cell growth and proliferation, vitellogenesis, and protein folding, stability and transport. Other genes down-regulated by E2, including those involved in acute-phase immune response, were also down-regulated by DIM and I3C. Gene regulation was confirmed by qRT-PCR and western blot. These data indicate I3C promotes hepatocarcinogenesis through estrogenic mechanisms in trout liver and suggest DIM may be an even more potent hepatic tumor promoter in this model.

Keywords: indole-3-carbinol; 3,3'-diindolylmethane; estradiol; gene expression; rainbow trout.
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
 Physiol. GenomicsHome page
F. W. Goetz, M. L. Rise, M. Rise, G. W. Goetz, F. Binkowski, and B. S. Shepherd
Stimulation of growth and changes in the hepatic transcriptome by 17{beta}-estradiol in the yellow perch (Perca flavescens)
Physiol Genomics, August 7, 2009; 38(3): 261 - 280.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. D. Benninghoff and D. E. Williams
Identification of a Transcriptional Fingerprint of Estrogen Exposure in Rainbow Trout Liver
Toxicol. Sci., January 1, 2008; 101(1): 65 - 80.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Kassie, L. B. Anderson, R. Scherber, N. Yu, D. Lahti, P. Upadhyaya, and S. S. Hecht
Indole-3-carbinol Inhibits 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Plus Benzo(a)pyrene-Induced Lung Tumorigenesis in A/J Mice and Modulates Carcinogen-Induced Alterations in Protein Levels
Cancer Res., July 1, 2007; 67(13): 6502 - 6511.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. C. Tilton, J. D. Hendricks, G. A. Orner, C. B. Pereira, G. S. Bailey, and D. E. Williams
Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout
Carcinogenesis, July 1, 2007; 28(7): 1589 - 1598.
[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.