CYP1A-dependent activation of xenobiotics in endothelial linings of the chorioallantoic membrane (CAM) in birds.
Metabolic activation of the heterocyclic amine 3-amino -1,4-dimethyl-5 H-pyrido[4,3-b]indole (Trp-P-1) and 7-ethoxyresorufin O-deethylase (EROD) activity were examined in the chorioallantoic membrane (CAM) of 15-day-old chicken and 18-day-old eider duck embryos. The embryos were pretreated with an Ah receptor agonist, i.e. beta-naphthoflavone (BNF) or 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or vehicle in ovo. BNF and PCB 126 induced EROD activity and covalent binding of [3H]Trp-P-1 seven- to tenfold in the CAM of chicken embryos. In the CAM of eider duck embryos, which are known to be nonresponsive to coplanar PCBs, PCB 126 treatment had no effect on EROD activity or covalent binding of [3H]Trp-P-1 whereas BNF treatment increased these activities five- and threefold, respectively. Light microscopic autoradiography was used to identify the cellular localization of covalent binding of [3H]Trp-P-1 in the CAM. Preferential binding was observed in endothelial cells in intraepithelial capillaries in the chorionic epithelium and in blood vessels in the mesenchymal layer. The addition of the CYP1A inhibitor ellipticine abolished the covalent binding of [3H]Trp-P-1 in the CAM of BNF- and PCB 126-treated chicken and eider duck embryos. The results suggest that CYP1A-dependent metabolic activity can be induced in blood vessel endothelia in the CAM of bird embryos following exposure to Ah receptor agonists and that the CAM may be a target tissue for CYP1A-activated environmental pollutants. Furthermore, the highly vascularized CAM could be used as a model for studies of Ah receptor-mediated alterations in the vasculature.
Annas
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A
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Brunström
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B
Brittebo
E B
EB
D000482:Allantois / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D000826:Animal Testing Alternatives; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology; D002243:Carbolines / Q000378:metabolism* / Q000633:toxicity; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004372:Ducks; D004611:Ellipticines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004790:Enzyme Induction; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000633:toxicity; D019324:beta-Naphthoflavone / Q000378:metabolism* / Q000633:toxicity
D002243:Carbolines; D004611:Ellipticines; C034192:ellipticine; D019324:beta-Naphthoflavone; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; C023035:3,4,5,3',4'-pentachlorobiphenyl