title: Catalytic and immunochemical properties of hepatic cytochrome P450 1A in three avian species treated with beta-naphthoflavone or isosafrole.
abstract: Induction of cytochrome P450 1A (CYP1A) can be used as a biomarker of exposure to planar halogenated aromatic hydrocarbons (PHAHs). Our objective was to characterize the induction of CYP1A activity and protein in three avian species following in vivo treatment with beta-naphthoflavone (BNF) and/or isosafrole. Alkoxyresorufin-O-dealkylase (alk-ROD) activities of hepatic microsomes from Herring Gulls (Larus argentatus) (HGs), Double-crested Cormorants (Phalacrocorax auritus) (DCCs) and chickens (Gallus domesticus) were measured using ethoxy-, methoxy-, pentoxy- and benzyloxy-resorufin, in the presence and absence of the inhibitors ellipticine or furafylline. Immunoreactivity of microsomal proteins with antibodies to several CYP1A proteins was investigated. CYP1A protein and alk-ROD activities of HGs and DCCs, but not chickens, were induced by isosafrole. Ellipticine was a potent and non-selective inhibitor of alk-ROD activity in all three species, while furafylline inhibition of alk-ROD activities varied among species and treatments. In all three species, BNF induced a protein immunoreactive with monoclonal antibody to CYP1A1 from the marine fish Stenotomus chrysops (scup), but a CYP1A2-like protein was not detected in avian microsomes probed with polyclonal antibodies to mouse CYP1A2. Variations in responses among avian species indicate that CYP1A proteins and substrate specificities should be characterized for each species used in PHAH biomonitoring programs.
authors.affiliation: Department of Fisheries and Wildlife, Pesticide Research Center and Institute for Environmental Toxicology, Michigan State University, East Lansing, MI 48824-1222, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Verbrugge
authors.forename: J P
authors.initials: JP
authors.lastname: Giesy
authors.forename: D A
authors.initials: DA
authors.lastname: Verbrugge
authors.forename: B R
authors.initials: BR
authors.lastname: Woodin
authors.forename: J J
authors.initials: JJ
authors.lastname: Stegeman
mesh_terms: D000818:Animals; D000906:Antibodies; D002384:Catalysis; D002645:Chickens; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000276:immunology / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004611:Ellipticines / Q000494:pharmacology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D015151:Immunoblotting; D007120:Immunochemistry; D012451:Safrole / Q000494:pharmacology*; D013045:Species Specificity; D019324:beta-Naphthoflavone / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004611:Ellipticines; D004791:Enzyme Inhibitors; C034192:ellipticine; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D012451:Safrole; C015959:isosafrole