Localization of cytochrome P4501A1 and covalent binding of a mutagenic heterocyclic amine in blood vessel endothelia of rodents.
Immunohistochemistry was used to examine the cellular localization of cytochrome P4501A1 (CYP1A1) in various types of endothelial linings in muscle tissues of rats and mice treated with the Ah receptor agonist beta-naphthoflavone (BNF). In addition, light microscopic autoradiography was used to localize sites of metabolic activation of 3H-labeled Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), a heterocyclic amine known to be metabolized by CYP1A1, in rodent tissue slices. The results showed a colocalization of CYP1A1 immunoreactivity and covalent binding of 3H-Trp-P-1 in endothelial linings of capillaries and veins of heart, skeletal muscle, and uterus in BNF-treated rodents, indicating the presence of catalytically active CYP1A1 at these sites. The immunohistochemical staining and covalent binding of 3H-Trp-P-1 in endothelia of arteries and arterioles was generally weak with the exception of uterine arterioles. In lymph nodes of BNF-treated rats, there was an intense CYP1A1 staining of high endothelial venules. The results suggest that endothelial linings of capillaries and veins in muscle tissues but also uterine arterioles and high endothelial venules in lymph nodes may be targets for CYP1A1-mediated metabolic products of endogenous and exogenous substances following exposure to CYP1A1 inducing agents.
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
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Brittebo
D000818:Animals; D001345:Autoradiography; D002243:Carbolines / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D009153:Mutagens / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone / Q000494:pharmacology
D002243:Carbolines; D009153:Mutagens; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole