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 autoradiogra phy was used to localize sites of metabolic activation of H-3-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 covalen t binding of H-3-Trp-P-1 in endothelial linings of capillaries and vei ns of heart, skeletal muscle, and uterus in BNF-treated rodents, indic ating the presence of catalytically active CYP1A1 at these sites. The immunohistochemical staining and covalent binding of H-3-Trp-P-1 in en dothelia of arteries and arterioles was generally weak with the except ion of uterine arterioles. In lymph nodes of BNF-treated rats, there w as an intense CYP1A1 staining of high endothelial venules. The results suggest that endothelial linings of capillaries and veins in muscle t issues but also uterine arterioles and high endothelial venules in lym ph nodes may be targets for CYP1A1-mediated metabolic products of endo genous and exogenous substances following exposure to CYP1A1 inducing agents. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.