Induction of ethoxyresorufin O-deethylase (EROD) and endothelial activation of the heterocyclic amine Trp-P-1 in bird embryo hearts.
The xenobiotic-metabolizing activity of avian heart was investigated in chicken and Eider duck embryos exposed to aryl hydrocarbon (Ah) receptor agonists in ovo. Both beta-naphthoflavone (BNF) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) induced 7-ethoxyresorufin O-deethylase (EROD) activities in chicken embryo hearts whereas Eider duck embryos only responded to BNF. The differential responses of chicken and Eider duck embryos were used to examine the involvement of Ah receptor-mediated enzyme induction in the activation of the environmental and food mutagen 3-amino- 1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1). As determined by light microscopic autoradiography, there was a highly selective binding of non-extractable 3H-Trp-P-1-derived radioactivity in endothelial cells of large vessels and capillaries in hearts of BNF- and PCB 126-treated chicken embryos. No binding occurred at these sites in vehicle-treated controls. There was also a strong endothelial binding of 3H-Trp-P-1 in hearts of BNF-treated Eider duck embryos whereas no binding occurred in hearts of PCB 126-treated Eider duck embryos. A positive correlation between induction of EROD activity and covalent binding of 3H-Trp-P-1 to protein in heart homogenates from BNF- and PCB 126-treated chicken and Eider duck embryos was also observed. The results suggest a cytochrome P450 1A (CYP1A)-mediated activation of Trp-P-1 in avian heart endothelial cells although involvement of other Ah receptor-regulated enzymes is also possible. We propose that heart endothelial cells may be targets for bioactivation and toxicity of environmental contaminants in birds exposed to Ah receptor agonists.
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
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Annas
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Brunström
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Brandt
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Brittebo
D000818:Animals; D001345:Autoradiography; D002243:Carbolines / Q000494:pharmacology*; D002642:Chick Embryo; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004372:Ducks / Q000196:embryology; D004727:Endothelium / Q000187:drug effects; D004790:Enzyme Induction; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D009206:Myocardium / Q000201:enzymology
D002243:Carbolines; D019363:Cytochrome P-450 CYP1A1; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole