Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression

B. D. Abbott, Gary H. Perdew, L. S. Birnbaum

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a family of halogenated aromatic hydrocarbons which are widespread environmental contaminants. In animals the adverse biological effects of TCDD include carcinogenesis, reproductive toxicity, immune function alteration, hyperkeratosis, hepatotoxicity, thymic involution, and teratogenesis. In the mouse embryo, TCDD induces cleft palate through a mechanism which involves altered differentiation and proliferation of the palatal cells, resulting in the failure of opposing shelves to fuse. Cleft palate induction by TCDD requires the Ah receptor. This study examines the expression of the Ah receptor in secondary palate of control and TCDD-exposed C57BL/6N embryos using in situ hybridization, Northern blots, and immunohistochemistry. Ah receptor protein expression was significantly higher in epithelial versus mesenchymal cells, and regional differences in expression within the epithelium were statistically significant. TCDD exposure was shown to downregulate Ah receptor mRNA and protein throughout the palatal shelf and this occurred at both the teratogenic dose and the dose which was not sufficient to produce cleft palate. This study represents the first demonstration of the tissue and cellular localization of the Ah receptor, raising questions about the extrapolation of results from cultured tumor cells to those observed in vivo.

Original languageEnglish (US)
Pages (from-to)16-25
Number of pages10
JournalToxicology and Applied Pharmacology
Volume126
Issue number1
DOIs
StatePublished - Jan 1 1994

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Aryl Hydrocarbon Receptors
Palate
Cleft Palate
Embryonic Structures
Halogenated Hydrocarbons
Teratogenesis
Cultured Tumor Cells
Aromatic Hydrocarbons
Electric fuses
Extrapolation
Northern Blotting
In Situ Hybridization
Toxicity
Polychlorinated Dibenzodioxins
1,4-dioxin
Tumors
Carcinogenesis
Animals
Proteins
Demonstrations

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

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abstract = "2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a family of halogenated aromatic hydrocarbons which are widespread environmental contaminants. In animals the adverse biological effects of TCDD include carcinogenesis, reproductive toxicity, immune function alteration, hyperkeratosis, hepatotoxicity, thymic involution, and teratogenesis. In the mouse embryo, TCDD induces cleft palate through a mechanism which involves altered differentiation and proliferation of the palatal cells, resulting in the failure of opposing shelves to fuse. Cleft palate induction by TCDD requires the Ah receptor. This study examines the expression of the Ah receptor in secondary palate of control and TCDD-exposed C57BL/6N embryos using in situ hybridization, Northern blots, and immunohistochemistry. Ah receptor protein expression was significantly higher in epithelial versus mesenchymal cells, and regional differences in expression within the epithelium were statistically significant. TCDD exposure was shown to downregulate Ah receptor mRNA and protein throughout the palatal shelf and this occurred at both the teratogenic dose and the dose which was not sufficient to produce cleft palate. This study represents the first demonstration of the tissue and cellular localization of the Ah receptor, raising questions about the extrapolation of results from cultured tumor cells to those observed in vivo.",
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Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression. / Abbott, B. D.; Perdew, Gary H.; Birnbaum, L. S.

In: Toxicology and Applied Pharmacology, Vol. 126, No. 1, 01.01.1994, p. 16-25.

Research output: Contribution to journalArticle

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