title: Differential expression, induction, and stability of CYP1A4 and CYP1A5 mRNA in chicken and herring gull embryo hepatocytes.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces cytochrome P4501A (CYP1A) catalyzed ethoxyresorufin-O-deethylase (EROD) activity in chickens and other avian species. To investigate mechanisms underlying the effectiveness of EROD activity as a biomarker for exposure to dioxin-like compounds in avian models, we characterized inter-species differences in isoform-specific CYP1A mRNA expression, induction, and stability in chickens (Gallus gallus domesticus) and herring gulls (Larus argentatus). Exposure to 100 nM TCDD significantly increased CYP1A4 and CYP1A5 mRNA expression in chicken and herring gull embryo hepatocyte cultures. Chicken CYP1A4 and CYP1A5 were induced 61-fold and 25-fold respectively. The herring gull isoforms were induced 2.2- and 4.3-fold respectively. In both species, the isoform that was preferentially induced exhibited lower constitutive expression. Half-lives of chicken CYP1A4, chicken CYP1A5, and herring gull CYP1A5 mRNA ranged from 5.0 to 7.0 h in cultured hepatocytes. The half-life of herring gull CYP1A4 mRNA was 2.5 h. Our findings indicate that expression, induction, and stability of CYP1A4 and CYP1A5 mRNA are differentially regulated in chickens and herring gulls. In particular, CYP1A4 is preferentially induced in chickens, while CYP1A5 is preferentially induced in herring gulls. We propose that CYP1A5 mRNA expression may be a sensitive biomarker of exposure to dioxin-like compounds in some avian species.
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Head
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D030161:Avian Proteins / Q000235:genetics*; D046091:Charadriiformes / Q000378:metabolism*; D002642:Chick Embryo; D002645:Chickens / Q000378:metabolism*; D004790:Enzyme Induction; D022781:Hepatocytes / Q000201:enzymology*; D010088:Oxidoreductases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis*; D013045:Species Specificity
chemical_list: D030161:Avian Proteins; D012333:RNA, Messenger; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C416342:CYP1A4 protein, Gallus gallus; C108015:cytochrome P-450 CYP1A5