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Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Phenobarbital on the Occurrence and Distribution of Four Cytochrome P-450 Isozymes in Rabbit Kidney, Lung, and Liver¹

Department of Biochemistry, The University of Texas Health Science Center at Dallas, Dallas, Texas 75235 [J. H. D., B. S. S. M], and Department of Biochemistry, Scripps Clinic and Research Foundation, La Jolla, California 92037 [U. M-E., E. F. J.]

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of phenobarbital (PB) on the distribution and occurrence of four 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 both untreated and PB-treated animals, while 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 of those studied found to be present 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 also 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. Our results indicate that, while PB altered the intensity of staining for Form 2 in the liver and kidney, TCDD altered both 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 both the kidney and lung which was not seen in either untreated or PB-pretreated rabbits.

¹ This work was supported by USPHS Grants HLBI 13619 and GM 16488.

² Recipient of USPHS Research Fellowship 5F32 HL-5684-03. To whom requests for reprints should be addressed.

³ Recipient of USPHS Grant HD 04445.

⁴ Recipient of USPHS Grant CA 24146.

Received 6/12/81. Accepted 12/ 2/81.

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