title: Dose and inducer-dependent induction of cytochrome P450 1A in endothelia of the eel, including in the swimbladder rete mirabile, a model microvascular structure.
abstract: Endothelium is a common site of cytochrome P450 1A (CYP1A) induction in vertebrates, and endothelial CYP1A could affect the distribution and toxicity of CYP1A substrates. We investigated CYP1A induction in organs rich in endothelium, gill, heart, and a microvascular model, the swimbladder rete mirabile, in the eel. Benzo[a]pyrene (BP) and 3, 3',4,4'-tetrachlorobiphenyl (TCB), radiolabeled and injected intraperitoneally, showed similar distribution in eels, with dose-dependent increases in concentration in heart and rete mirabile. BP [given at 0.1, 1, and 10 mg/kg (0.4, 4, and 40 micromol/kg)], TCB [given at 0.1, 1, and 10 mg/kg (0.3, 3, 30, and 60 micromol/kg)], and beta-naphthoflavone (BNF) [given at 0.1, 1, 5, 10, and 100 mg/kg (0.4, 4, 20, 40, and 400 micromol/kg)] induced microsomal CYP1A and ethoxyresorufin O-deethylase in heart and rete mirabile. Immunohistochemical analysis confirmed that induction of CYP1A in heart and rete mirabile occurs in the endothelium. Increasing doses of each compound caused increasing penetration of induction into the vascular bed of the rete, but with BNF and BP induction penetrated further than with TCB. At high doses of BNF there also was induction in epithelial cells adjacent to endothelium in gill and kidney. CYP1A also was induced in heart and rete mirabile of eels from sites heavily contaminated by aryl hydrocarbon receptor (AHR) agonists. The penetration of CYP1A induction into capillaries of the rete mirabile reflects the penetration of the inducer itself, consistent with the idea that endothelial CYP1A can indicate the local distribution of AHR agonists. The microvascular rete mirabile in the eel provides a model system to explore further a hypothesis that endothelial CYP1A participates in removal of some AHR agonists from the circulation and to examine the consequences of CYP1A induction to the vascular system.
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Schlezinger
authors.forename: J J
authors.initials: JJ
authors.lastname: Stegeman
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004524:Eels; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D004790:Enzyme Induction; D005880:Gills / Q000201:enzymology* / Q000378:metabolism; D006321:Heart / Q000502:physiology; D007150:Immunohistochemistry; D008833:Microcirculation / Q000187:drug effects; D008861:Microsomes / Q000201:enzymology* / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl