ToxSci Advance Access originally published online on September 7, 2006
Toxicological Sciences 2006 94(2):398-416; doi:10.1093/toxsci/kfl100
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Comparative Toxicogenomic Analysis of the Hepatotoxic Effects of TCDD in Sprague Dawley Rats and C57BL/6 Mice
,,1
* Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824
Center for Integrative Toxicology, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824
Wellington Laboratories Inc., Guelph, Ontario N1G 3M5, Canada
Department of Pathobiology and Diagnostic Investigation, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824
¶ Gene Logic Inc., Gaithersburg, Maryland 20879
Received July 12, 2006; accepted September 1, 2006
In an effort to further characterize conserved and species-specific mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)–mediated toxicity, comparative temporal and dose-response microarray analyses were performed on hepatic tissue from immature, ovariectomized Sprague Dawley rats and C57BL/6 mice. For temporal studies, rats and mice were gavaged with 10 or 30 µg/kg of TCDD, respectively, and sacrificed after 2, 4, 8, 12, 18, 24, 72, or 168 h while dose-response studies were performed at 24h. Hepatic gene expression profiles were monitored using custom cDNA microarrays containing 8567 (rat) or 13,361 (mouse) cDNA clones. Affymetrix data from male rats treated with 40 µg/kg TCDD were also included to expand the species comparison. In total, 3087 orthologous genes were represented in the cross-species comparison. Comparative analysis identified 33 orthologous genes that were commonly regulated by TCDD as well as 185 rat-specific and 225 mouse-specific responses. Functional annotation using Gene Ontology identified conserved gene responses associated with xenobiotic/chemical stress and amino acid and lipid metabolism. Rat-specific gene expression responses were associated with cellular growth and lipid metabolism while mouse-specific responses were associated with lipid uptake/metabolism and immune responses. The common and species-specific gene expression responses were also consistent with complementary histopathology, clinical chemistry, hepatic lipid analyses, and reports in the literature. These data expand our understanding of TCDD-mediated gene expression responses and indicate that species-specific toxicity may be mediated by differences in gene expression which may help explain the wide range of species sensitivities and will have important implications in risk assessment strategies.
Key Words: TCDD; toxicogenomics; liver; cross-species comparison.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. D. Burgoon, Q. Ding, A. N'jai, E. Dere, A. R. Burg, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Automated Dose-Response Analysis of the Relative Hepatic Gene Expression Potency of TCDF in C57BL/6 Mice Toxicol. Sci., November 1, 2009; 112(1): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kim, E. Dere, L. D. Burgoon, C.-C. Chang, and T. R. Zacharewski Comparative Analysis of AhR-Mediated TCDD-Elicited Gene Expression in Human Liver Adult Stem Cells Toxicol. Sci., November 1, 2009; 112(1): 229 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Carlson, C. McCulloch, A. Koganti, S. B. Goodwin, T. R. Sutter, and J. B. Silkworth Divergent Transcriptomic Responses to Aryl Hydrocarbon Receptor Agonists between Rat and Human Primary Hepatocytes Toxicol. Sci., November 1, 2009; 112(1): 257 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Boutros, K. A. Bielefeld, R. Pohjanvirta, and P. A. Harper Dioxin-Dependent and Dioxin-Independent Gene Batteries: Comparison of Liver and Kidney in AHR-Null Mice Toxicol. Sci., November 1, 2009; 112(1): 245 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N'Jai, D. R. Boverhof, E. Dere, L. D. Burgoon, Y. S. Tan, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Comparative Temporal Toxicogenomic Analysis of TCDD- and TCDF-Mediated Hepatic Effects in Immature Female C57BL/6 Mice Toxicol. Sci., June 1, 2008; 103(2): 285 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. K. Kopec, D. R. Boverhof, L. D. Burgoon, D. Ibrahim-Aibo, J. R. Harkema, C. Tashiro, B. Chittim, and T. R. Zacharewski Comparative Toxicogenomic Examination of the Hepatic Effects of PCB126 and TCDD in Immature, Ovariectomized C57BL/6 Mice Toxicol. Sci., March 1, 2008; 102(1): 61 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sarioglu, S. Brandner, M. Haberger, C. Jacobsen, J. Lichtmannegger, M. Wormke, and U. Andrae Analysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Proteome Changes in 5L Rat Hepatoma Cells Reveals Novel Targets of Dioxin Action Including the Mitochondrial Apoptosis Regulator VDAC2 Mol. Cell. Proteomics, February 1, 2008; 7(2): 394 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Moffat, P. C. Boutros, T. Celius, J. Linden, R. Pohjanvirta, and A. B. Okey microRNAs in Adult Rodent Liver Are Refractory to Dioxin Treatment Toxicol. Sci., October 1, 2007; 99(2): 470 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Okey An Aryl Hydrocarbon Receptor Odyssey to the Shores of Toxicology: The Deichmann Lecture, International Congress of Toxicology-XI Toxicol. Sci., July 1, 2007; 98(1): 5 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Walker Unraveling the Complexities of the Mechanism of Action of Dioxins Toxicol. Sci., February 1, 2007; 95(2): 297 - 299. [Full Text] [PDF]
|
|