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ToxSci Advance Access originally published online on June 15, 2005
Toxicological Sciences 2005 88(1):60-72; doi:10.1093/toxsci/kfi228
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© 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.


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