![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication September 8, 2005.
Revised October 3, 2005.
Accepted for publication October 7, 2005.
ABSTRACT Conventional biochemical and molecular techniques previously identified several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahr-/-) with those in mice with wildtype AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 hours earlier with 1000 µg/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classical AHRE-I gene battery such as Cyp1a1, Cyp1a2, Cyp1b1 and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahr-/-, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, previously considered uninducible, were highly induced by TCDD in an AHR-dependent manner. Intriguingly, the estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively-studied AHR and ER pathways. p53 binding sites are over-represented in genes downregulated by TCDD suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR either for constitutive expression or for response to TCDD.
Key words:
Sex hormones, Regulation of gene expression, Cytochrome P450, Flavin monooxygenases, Regulation - transcriptional, Regulation - xenobiotic, Ah receptor, Toxicant-induced gene express
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
R. L. Yeager, S. A. Reisman, L. M. Aleksunes, and C. D. Klaassen Introducing the "TCDD-Inducible AhR-Nrf2 Gene Battery" Toxicol. Sci., October 1, 2009; 111(2): 238 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Novick, A. M. Mitzey, M. S. Brownfield, and A. A. Elfarra Differential Localization of Flavin-Containing Monooxygenase (FMO) Isoforms 1, 3, and 4 in Rat Liver and Kidney and Evidence for Expression of FMO4 in Mouse, Rat, and Human Liver and Kidney Microsomes J. Pharmacol. Exp. Ther., June 1, 2009; 329(3): 1148 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Kransler, B. P. McGarrigle, D. D. Swartz, and J. R. Olson Lung Development in the Holtzman Rat is Adversely Affected by Gestational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Toxicol. Sci., February 1, 2009; 107(2): 498 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Celius, S. Roblin, P. A. Harper, J. Matthews, P. C. Boutros, R. Pohjanvirta, and A. B. Okey Aryl Hydrocarbon Receptor-Dependent Induction of Flavin-Containing Monooxygenase mRNAs in Mouse Liver Drug Metab. Dispos., December 1, 2008; 36(12): 2499 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Novick and A. A. Elfarra Purification and Characterization of Flavin-Containing Monooxygenase Isoform 3 from Rat Kidney Microsomes Drug Metab. Dispos., December 1, 2008; 36(12): 2468 - 2474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Simon, C. R. Kirman, L. L. Aylward, R. A. Budinsky, J. C. Rowlands, and T. F. Long Estimates of Cancer Potency of 2,3,4,7,8-Pentachlorodibenzofuran Using Both Nonlinear and Linear Approaches Toxicol. Sci., December 1, 2008; 106(2): 519 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. M. Staal, D. S. Pushparajah, M. H. M. van Herwijnen, R. W. H. Gottschalk, L. M. Maas, C. Ioannides, F. J. van Schooten, and J. H. M. van Delft Interactions between polycyclic aromatic hydrocarbons in binary mixtures: Effects on gene expression and DNA adduct formation in precision-cut rat liver slices Mutagenesis, November 1, 2008; 23(6): 491 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Sawaya and D. S. Riddick Cytochrome P450 2C11 5'-Flanking Region and Promoter Mediate in Vivo Suppression by 3-Methylcholanthrene Drug Metab. Dispos., September 1, 2008; 36(9): 1803 - 1811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hudder and R. F. Novak miRNAs: Effectors of Environmental Influences on Gene Expression and Disease Toxicol. Sci., June 1, 2008; 103(2): 228 - 240. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. Shin, N. Wakabayashi, V. Misra, S. Biswal, G. H. Lee, E. S. Agoston, M. Yamamoto, and T. W. Kensler NRF2 Modulates Aryl Hydrocarbon Receptor Signaling: Influence on Adipogenesis Mol. Cell. Biol., October 15, 2007; 27(20): 7188 - 7197. [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]
|
|
|
|
 |
|
 I. D. Moffat, S. Roblin, P. A. Harper, A. B. Okey, and R. Pohjanvirta Aryl Hydrocarbon Receptor Splice Variants in the Dioxin-Resistant Rat: Tissue Expression and Transactivational Activity Mol. Pharmacol., October 1, 2007; 72(4): 956 - 966. [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]
|
|
|
|
 |
|
 C. G. Woods, J. P. Vanden Heuvel, and I. Rusyn Genomic Profiling in Nuclear Receptor-Mediated Toxicity Toxicol Pathol, June 1, 2007; 35(4): 474 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Koukouritaki, M. T. Poch, M. C. Henderson, L. K. Siddens, S. K. Krueger, J. E. VanDyke, D. E. Williams, N. M. Pajewski, T. Wang, and R. N. Hines Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 266 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Ovando, C. M. Vezina, B. P. McGarrigle, and J. R. Olson Hepatic Gene Downregulation following Acute and Subchronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicol. Sci., December 1, 2006; 94(2): 428 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pastorelli, D. Carpi, R. Campagna, L. Airoldi, R. Pohjanvirta, M. Viluksela, H. Hakansson, P. C. Boutros, I. D. Moffat, A. B. Okey, et al. Differential Expression Profiling of the Hepatic Proteome in a Rat Model of Dioxin Resistance: CORRELATION WITH GENOMIC AND TRANSCRIPTOMIC ANALYSES Mol. Cell. Proteomics, May 1, 2006; 5(5): 882 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ishimura, T. Kawakami, S. Ohsako, K. Nohara, and C. Tohyama Suppressive Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Vascular Remodeling That Takes Place in the Normal Labyrinth Zone of Rat Placenta during Late Gestation Toxicol. Sci., May 1, 2006; 91(1): 265 - 274. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
