Dose and inducer-dependent induction of cytochrome P450 1A in endothelia of the eel, including in the swimbladder rete mirabile, a model microvascular structure

Endothelium is a common site of cytochrome P450 1A (CYP1A) induction in ver tebrates, and endothelial CYP1A could affect the distribution and toxicity of CYP1A substrates. We investigated CYP1A induction in organs rich in endo thelium, gill, heart, and a microvascular model, the swimbladder rete mirab ile, in the eel. Benzo[ a] pyrene (BP) and 3,3',4,4'-tetrachlorobiphenyl (T CB), radiolabeled and injected intraperitoneally, showed similar distributi on in eels, with dose-dependent increases in concentration in heart and ret e mirabile. BP [given at 0.1, 1, and 10 mg/kg (0.4, 4, and 40 mu mol/kg)], TCB [given at 0.1, 1, and 10 mg/kg (0.3, 3, 30, and 60 mu mol/kg)], and bet a-naphthoflavone (BNF) [given at 0.1, 1, 5, 10, and 100 mg/kg (0.4, 4, 20, 40, and 400 mu mol/kg)] induced microsomal CYP1A and ethoxyresorufin O-deet hylase in heart and rete mirabile. Immunohistochemical analysis confirmed t hat induction of CYP1A in heart and rete mirabile occurs in the endothelium . Increasing doses of each compound caused increasing penetration of induct ion into the vascular bed of the rete, but with BNF and BP induction penetr ated further than with TCB. At high doses of BNF there also was induction i n epithelial cells adjacent to endothelium in gill and kidney. CYP1A also w as induced in heart and rete mirabile of eels from sites heavily contaminat ed by aryl hydrocarbon receptor (AHR) agonists. The penetration of CYP1A in duction into capillaries of the rete mirabile reflects the penetration of t he inducer itself, consistent with the idea that endothelial CYP1A can indi cate the local distribution of AHR agonists. The microvascular rete mirabil e in the eel provides a model system to explore further a hypothesis that e ndothelial CYP1A participates in removal of some AHR agonists from the circ ulation and to examine the consequences of CYP1A induction to the vascular system.