Skip Navigation



ToxSci Advance Access published online on August 24, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi301
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
88/1/231    most recent
kfi301v1
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 Thackaberry, E.A.
Right arrow Articles by Walker, M.K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thackaberry, E.A.
Right arrow Articles by Walker, M.K.
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@oupjournals.org
Received July 21, 2005
Accepted August 22, 2005

Reproductive and Developmental Toxicology

Toxicogenomic Profile of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Murine Fetal Heart: Modulation of Cell Cycle and Extracellular Matrix Genes

E.A. Thackaberry 1, Z. Jiang 2, C.D. Johnson 3, K.S. Ramos 4, and M.K. Walker 5*

1 University of New Mexico Health Sciences Center, College of Pharmacy, Albuquerque, NM 87131
2 University of New Mexico Health Sciences Center, Department of Biocomputing, Albuquerque, NM 87131
3 Ambion, Inc. The RNA Company, Austin, TX 78744
4 Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292
5 University of New Mexico Health Sciences Center, College of Pharmacy, Albuquerque, NM 87131; University of New Mexico Health Sciences Center, Department of Cell Biology and Physiology, Albuquerque, NM 87131

* To whom correspondence should be addressed.
M.K. Walker, E-mail: mkwalker{at}unm.edu


  Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and similar environmental contaminants have been demonstrated previously to be potent cardiovascular teratogens in developing piscine and avian species. In the current study, we investigated the effects of TCDD on gene expression during murine cardiovascular development. C57Bl6N pregnant mice were dosed with 1.5, 3.0, or 6.0 µg TCDD/kg on gestation day (GD) 14.5, and microarray analysis was used to characterize the global changes in fetal cardiac gene expression on GD17.5. TCDD significantly altered expression of a number of genes involved in xenobiotic metabolism, cardiac homeostasis, extracellular matrix production/remodeling, and cell cycle regulation. Interestingly, while the AhR-responsive genes Cyp1A1, Cyp1B1, Ugt1a6, and Ahrr, were all induced by TCDD in the fetal murine heart, other AhR-responsive genes, Cyp1a2, Nqo1 and Gsta1, were not. Quantitative real-time PCR confirmed the changes in expression of several G1/S-type cyclins and extracellular matrix-related genes. These results demonstrate the global changes in cardiac gene expression that result from TCDD exposure of the fetal murine heart and implicate genes involved in cell cycle and extracellular matrix regulation in TCDD-induced cardiac teratogenicity and functional deficits.

Keywords: TCDD; aryl hydrocarbon receptor; microarray; heart development; cell cycle.
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
S. P. Jones and S. W. Kennedy
Chicken Embryo Cardiomyocyte Cultures--A New Approach for Studying Effects of Halogenated Aromatic Hydrocarbons in the Avian Heart
Toxicol. Sci., May 1, 2009; 109(1): 66 - 74.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. M. Billiard, J. N. Meyer, D. M. Wassenberg, P. V. Hodson, and R. T. Di Giulio
Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment
Toxicol. Sci., September 1, 2008; 105(1): 5 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
V. Mehta, R. E. Peterson, and W. Heideman
2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure Prevents Cardiac Valve Formation in Developing Zebrafish
Toxicol. Sci., August 1, 2008; 104(2): 303 - 311.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. B. Silkworth, E. A. Carlson, C. McCulloch, K. Illouz, S. Goodwin, and T. R. Sutter
Toxicogenomic Analysis of Gender, Chemical, and Dose Effects in Livers of TCDD- or Aroclor 1254-Exposed Rats Using a Multifactor Linear Model
Toxicol. Sci., April 1, 2008; 102(2): 291 - 309.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. C. Aragon, P. G. Kopf, M. J. Campen, J. K. Huwe, and M. K. Walker
In Utero and Lactational 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure: Effects on Fetal and Adult Cardiac Gene Expression and Adult Cardiac and Renal Morphology
Toxicol. Sci., February 1, 2008; 101(2): 321 - 330.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. E. Jonsson, M. J. Jenny, B. R. Woodin, M. E. Hahn, and J. J. Stegeman
Role of AHR2 in the Expression of Novel Cytochrome P450 1 Family Genes, Cell Cycle Genes, and Morphological Defects in Developing Zebra Fish Exposed to 3,3',4,4',5-Pentachlorobiphenyl or 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Toxicol. Sci., November 1, 2007; 100(1): 180 - 193.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
E. A. Andreasen, L. K. Mathew, C. V. Lohr, R. Hasson, and R. L. Tanguay
Aryl Hydrocarbon Receptor Activation Impairs Extracellular Matrix Remodeling during Zebra Fish fin Regeneration
Toxicol. Sci., January 1, 2007; 95(1): 215 - 226.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. A. Carney, J. Chen, C. G. Burns, K. M. Xiong, R. E. Peterson, and W. Heideman
Aryl Hydrocarbon Receptor Activation Produces Heart-Specific Transcriptional and Toxic Responses in Developing Zebrafish
Mol. Pharmacol., August 1, 2006; 70(2): 549 - 561.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
E. A. Andreasen, L. K. Mathew, and R. L. Tanguay
Regenerative Growth Is Impacted by TCDD: Gene Expression Analysis Reveals Extracellular Matrix Modulation
Toxicol. Sci., July 1, 2006; 92(1): 254 - 269.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
L. K. Mathew, E. A. Andreasen, and R. L. Tanguay
Aryl Hydrocarbon Receptor Activation Inhibits Regenerative Growth
Mol. Pharmacol., January 1, 2006; 69(1): 257 - 265.
[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.