Differential induction of two 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible forms of cytochrome P-450 in extrahepatic versus hepatic tissues.

The present study examines the induction of two isozymes of cytochrome P-450, P-448HCB and P-448MC, by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in hepatic and a number of extrahepatic tissues of male rats. These isozymes were quantitated by radioimmunoassay (RIA). TCDD induces both forms of cytochrome P-448 markedly in liver. In extrahepatic tissues, TCDD induces cytochrome P-448MC but not cytochrome P-448HCB. Induction of cytochrome P-448MC is greatest in liver greater than kidney greater than lung greater than intestine greater than spleen greater than testes greater than brain (no significantly increased). The results in liver, kidney, and lung were confirmed by a technique that depends on both electrophoretic mobility and immunological characteristics (sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by transfer to nitrocellulose paper and immunostaining of the protein). Cytochrome P-448HCB is a minor constitutive form in livers of control male rats (5% of the total cytochrome P-450). In contrast, cytochrome P-448MC is below the level of detection in control livers using the immunostaining technique (less than 0.6% by RIA). These results indicate that induction of cytochrome P-450 isozymes by TCDD is tissue-dependent in the rat. The response of extrahepatic tissues to TCDD is more limited than that of liver.