Skip Navigation


ToxSci Advance Access originally published online on June 15, 2005
Toxicological Sciences 2005 88(1):60-72; doi:10.1093/toxsci/kfi228
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
88/1/60    most recent
kfi228v1
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lavine, J. A.
Right arrow Articles by Powell, W. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lavine, J. A.
Right arrow Articles by Powell, W. H.
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

Aryl Hydrocarbon Receptors in the Frog Xenopus laevis: Two AhR1 Paralogs Exhibit Low Affinity for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

Jeremy A. Lavine, Ashley J. Rowatt, Tatyana Klimova, Aric J. Whitington, Emelyne Dengler, Catherine Beck and Wade H. Powell1

Biology Department, Kenyon College, Gambier, Ohio 43022

Received May 17, 2005; accepted June 2, 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates. However, frogs are relatively insensitive to TCDD toxicity, especially during early life stages. Toxicity of TCDD and related halogenated aromatic hydrocarbons is mediated by the aryl hydrocarbon receptor (AhR), and specific differences in properties of the AhR signaling pathway can underlie in TCDD toxicity in different species. This study investigated the role of AhR in frog TCDD insensitivity, using Xenopus laevis as a model system. X. laevis, a pseudotetraploid species, expresses two distinct AhR1 genes, AhR1{alpha} and AhR1ß. Sharing 86% amino acid identity, these likely represent distinct genes, both orthologous to mammalian AhR and paralogous to the AhR2 gene(s) in most fish. Both AhR1{alpha} and AhR1ß exhibit TCDD-dependent binding of cognate DNA sequences, but they bind TCDD with at least 20-fold lower affinity than the mouse AhRb–1 protein, and they are similarly less responsive in TCDD-induced reporter gene induction in conjunction with the mouse CYP1A1 promoter. Furthermore, CYP1A6 and CYP1A7 induction by TCDD in cultured X. laevis A6 cells appears much less responsive than CYP1A induction in cell lines derived from more sensitive animals. Taken together, these data suggest that low affinity binding by X. laevis AhRs plays an important mechanistic role in the insensitivity of frogs to TCDD. An understanding of these molecular mechanisms should aid amphibian ecotoxicology and refine the use of frog embryos as a model [e.g. in FETAX (Frog Embryo Teratogenesis Assay-Xenopus)] for determining developmental toxicity of samples containing dioxin-like compounds.

Key Words: aryl hydrocarbon receptors; TCDD; Xenopus laevis; FETAX.


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
A. L. Zimmermann, E. A. King, E. Dengler, S. R. Scogin, and W. H. Powell
An Aryl Hydrocarbon Receptor Repressor from Xenopus laevis: Function, Expression, and Role in Dioxin Responsiveness during Frog Development
Toxicol. Sci., July 1, 2008; 104(1): 124 - 134.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. W. Hornung, P. M. Cook, P. N. Fitzsimmons, D. W. Kuehl, and J. W. Nichols
Tissue Distribution and Metabolism of Benzo[a]pyrene in Embryonic and Larval Medaka (Oryzias latipes)
Toxicol. Sci., December 1, 2007; 100(2): 393 - 405.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. I. Karchner, D. G. Franks, S. W. Kennedy, and M. E. Hahn
The molecular basis for differential dioxin sensitivity in birds: Role of the aryl hydrocarbon receptor
PNAS, April 18, 2006; 103(16): 6252 - 6257.
[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.