EFFECT OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AND PHENOBARBITAL ON THE OCCURRENCE AND DISTRIBUTION OF 4 CYTOCHROME-P-450 ISOZYMES IN RABBIT KIDNEY, LUNG, AND LIVER

Abstract

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of phenobarbital (PB) on the distribution and occurrence of 4 cytochrome P-450 isozymes(forms 2, 3, 4 and 6) in the kidney, lung and liver of adult male rabbits was investigated using immunofluorescence. In the kidney forms 2 and 3 were localized in the proximal tubules of untreated and PB-treated animals, whereas antibodies to forms 4 and 6 showed weak to negative staining. In TCDD-pretreated animals, forms 4 and 6 appeared in the renal endothelium, in addition to staining the proximal tubular epithelium intensely. Form 2 was the only isoenzyme found in the lungs of normal and PB-pretreated rabbits; it was also present in lungs of TCDD-pretreated rabbits. Form 3 was not detected in any of the rabbit lungs examined. Forms 4 and 6, while not apparent in the lungs of normal or PB-treated animals, were found in the lungs of TCDD-treated animals and appeared in the endothelium of the pulmonary arteries and veins. All forms tested were present in control liver. The staining for form 2 was intense in the livers of PB-pretreated animals as was the staining for forms 4 and 6 in the livers of TCDD-pretreated animals. Whereas PB altered the intensity of staining for form 2 in the liver and kidney, TCDD altered the staining intensity and distribution of the isozymes in kidney, lung and liver, producing, for example, a localization of forms 4 and 6 in the endothelium of the kidney and lung which was not seen in untreated or PB-pretreated rabbits. [The cytochrome P-450 isozymes have been implicated in the metabolic activator of a wide variety of chemical carcinogens.].