title: Hepatic microsomal ethoxyresorufin O-deethylase-inducing potency in ovo and cytosolic Ah receptor binding affinity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: comparison of four avian species.
abstract: The hepatic microsomal ethoxyresorufin O-deethylase (EROD)-inducing potency in ovo of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was determined in the domestic chicken (Gallus gallus), domestic pigeon (Columba livia), great blue heron, and double-crested cormorant. Dose-response curves were produced by injecting various doses of [3H]TCDD into the air sac of developing eggs during the latter third part of incubation. Hepatic EROD activities were measured in day-old hatchlings. Liver, yolk, and whole blood were analyzed for [3H]TCDD; no distributional differences among species were found. The ED50 for EROD induction was between one and two orders of magnitude lower in the chick (0.1 microgram/kg egg) than in the heron and cormorant (3-10 micrograms/kg egg). Consistent with this, the apparent affinity of TCDD for the hepatic cytosolic Ah receptor was about 15 times higher in the domestic chick (Kd = 0.75-1.6) than in the other avian species (pigeon, Kd = 11-14; heron, Kd = 10-20; cormorant, Kd = 12-16). Receptor binding affinities in the pigeon, heron, and cormorant were of the same order of magnitude as that reported for human placenta (D.K. Manchester, S.K. Gordon, C.L. Golas, E.A. Roberts, and A.B. Okey, 1987, Cancer Res. 47, 4861-4868). Subcutaneous edema was observed in TCDD-treated hatchlings of the chick, heron, and cormorant, but not of the pigeon, within the dose range examined. The laboratory dose-response relationships demonstrated that the heron and cormorant hatchlings that were exposed to TCDD and related chemicals in the Strait of Georgia (J.T. Sanderson, R.J. Norstrom, J.E. Elliott, L.E. Hart, K.M. Cheng, and G.D. Bellward (1994b) J. Toxicol. Environ. Health 41, 245-263; and J.T. Sanderson, J.E. Elliott, R.J. Norstrom, P.E. Whitehead, L.E. Hart, K.M. Cheng, and G.D. Bellward (1994a) J. Toxicol. Environ. Health 41, 435-450) had hepatic EROD activities at the lower end of the linear part of their respective dose-response curves. A further increase in levels of TCDD and related compounds in the environment would lead to a large increase in EROD activity and further increases in TCDD-induced toxicities, such as body weight loss and subcutaneous edema.
authors.affiliation: Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: J T
authors.initials: JT
authors.lastname: Sanderson
authors.forename: G D
authors.initials: GD
authors.lastname: Bellward
mesh_terms: D000818:Animals; D001715:Bird Diseases / Q000139:chemically induced; D001717:Birds / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D010856:Columbidae / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000662:veterinary; D015151:Immunoblotting; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1