Formation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene adducts in vascular endothelia of cytochrome P4501A-induced chicken embryos.

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and birds may be exposed to PAHs via diet, from preening feathers contaminated with oil, or through contamination of the eggshell during embryo development. In the present study, tissue distribution and the cell-specific binding of two labeled PAHs, benzo[a]pyrene ([3H]BaP) and 7,12-dimethylbenz[a]anthracene ([3H]DMBA), were examined in chicken embryos exposed in ovo to CYP1A inducers. Tape-section autoradiograms revealed high concentrations of radioactivity in the bile, liver, kidneys, heart, and leptomeninges.

CYP1A1 and CYP1B1 in blood-brain interfaces: CYP1A1-dependent bioactivation of 7,12-dimethylbenz(a)anthracene in endothelial cells.

Immunohistochemistry and autoradiography were used to identify sites of the cytochrome P450 enzymes (P450) 1A1 and 1B1 expression and activation of 7,12-dimethylbenz(a)anthracene (DMBA), in the brain of rodents pretreated with the aryl hydrocarbon receptor (AhR) agonists beta-naphthoflavone (BNF), 3,3',4,4',5-pentachlorobiphenyl or vehicle. Immunohistochemistry revealed that CYP1A1 was preferentially induced in endothelial cells (EC) in the choroid plexus, in veins in the leptomeninges, and in cerebral veins of AhR agonist-pretreated mice. No induction occurred in cerebral capillary EC.

Target cells for cytochrome p450-catalysed irreversible binding of 7,12-dimethylbenz[a]anthracene (DMBA) in rodent adrenal glands.

7,12-Dimethylbenz[a]anthracene (DMBA) is an adrenocorticolytic agent that causes apoplexy (haemorrhage) and massive necrosis in the adrenal cortex in rat. Several explanations regarding the origin of toxicity have been proposed. Huggins and Morii (J Exp Med 114:741-60, 1961) suggested that the cells of the inner adrenal cortex are the primary target, whereas Horváth and Kovács (Pathol Eur 8:43-59, 1973) suggested the vascular endothelium as being the origin of toxicity.