title: Formation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene adducts in vascular endothelia of cytochrome P4501A-induced chicken embryos.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and birds may be exposed to PAHs via diet, from preening feathers contaminated with oil, or through contamination of the eggshell during embryo development. In the present study, tissue distribution and the cell-specific binding of two labeled PAHs, benzo[a]pyrene ([3H]BaP) and 7,12-dimethylbenz[a]anthracene ([3H]DMBA), were examined in chicken embryos exposed in ovo to CYP1A inducers. Tape-section autoradiograms revealed high concentrations of radioactivity in the bile, liver, kidneys, heart, and leptomeninges. Light microscopy autoradiography of solvent-extracted tissue slices showed a high and selective binding in endothelial cells in certain blood vessels in brain, heart, lung, and chest muscle. Binding was also observed in blood vessel endothelial cells in the chorioallantoic membrane (CAM), an extraembryonal tissue lining the eggshell. Endothelial binding was confirmed in CAM exposed in vitro, implying that tissue-binding metabolites were formed in situ. The CYP1A inhibitor ellipticine abolished bleeding in the target endothelial cells in CAM. It is thus concluded that blood vessel endothelia in various tissues in birds can bioactivate environmental contaminants and be targets for their toxicity. In view of its critical position beneath the shell, the CAM could be an important target for toxicants following external exposure in oviparous species.
authors.affiliation: Department of Environmental Toxicology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18 A, SE-752 36 Uppsala, Sweden.
authors.forename: Lizette
authors.initials: L
authors.lastname: Granberg
authors.forename: Björn
authors.initials: B
authors.lastname: Brunström
authors.forename: Ingvar
authors.initials: I
authors.lastname: Brandt
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000494:pharmacology*; D001551:Benz(a)Anthracenes / Q000378:metabolism* / Q000493:pharmacokinetics*; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000493:pharmacokinetics*; D002642:Chick Embryo; D004611:Ellipticines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014018:Tissue Distribution; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D001551:Benz(a)Anthracenes; D004611:Ellipticines; D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; C034192:ellipticine; C046810:7,12-dihydroxymethylbenz(a)anthracene; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases