Goldstein J A, Linko P
Mol Pharmacol. 1984 Jan;25(1):185-91.
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.
本研究检测了2,3,7,8-四氯二苯并对二恶英（TCDD）对雄性大鼠肝脏及一些肝外组织中细胞色素P-450的两种同工酶P-448HCB和P-448MC的诱导作用。这些同工酶通过放射免疫分析（RIA）进行定量。TCDD在肝脏中显著诱导两种形式的细胞色素P-448。在肝外组织中，TCDD诱导细胞色素P-448MC，但不诱导细胞色素P-448HCB。细胞色素P-448MC的诱导在肝脏中最大，其次是肾脏、肺、肠道、脾脏、睾丸、大脑（无显著增加）。肝脏、肾脏和肺中的结果通过一种依赖于电泳迁移率和免疫学特性的技术得到证实（十二烷基硫酸钠-聚丙烯酰胺凝胶电泳，随后转移到硝酸纤维素纸上并对蛋白质进行免疫染色）。细胞色素P-448HCB是对照雄性大鼠肝脏中的一种次要组成形式（占细胞色素P-450总量的5%）。相比之下，使用免疫染色技术在对照肝脏中细胞色素P-448MC低于检测水平（RIA检测小于0.6%）。这些结果表明，TCDD对细胞色素P-450同工酶的诱导在大鼠中具有组织依赖性。肝外组织对TCDD的反应比肝脏更有限。
