title: Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: comparisons with AHR1-mediated reporter gene activity and in ovo toxicity.
abstract: Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species.
authors.affiliation: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5. gmann017@uottawa.ca
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Manning
authors.forename: Lukas J
authors.initials: LJ
authors.lastname: Mundy
authors.forename: Doug
authors.initials: D
authors.lastname: Crump
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Jones
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chiu
authors.forename: Jeff
authors.initials: J
authors.lastname: Klein
authors.forename: Alex
authors.initials: A
authors.lastname: Konstantinov
authors.forename: Dave
authors.initials: D
authors.lastname: Potter
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D001717:Birds; D002478:Cells, Cultured; D002645:Chickens; D003370:Coturnix; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D011078:Polychlorinated Biphenyls; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C108015:cytochrome P-450 CYP1A5