Wolff T, Guengerich F P
Biochem Pharmacol. 1987 Aug 15;36(16):2581-8. doi: 10.1016/0006-2952(87)90535-1.
To explore which rat liver cytochrome P-450 species are involved in aldrin epoxidation, we have studied the catalytic activities of a series of cytochrome P-450 isozymes purified from untreated and inducer-treated Sprague-Dawley rats. Of ten cytochrome P-450 forms analyzed, seven isozymes, listed in order of decreasing activity, catalyzed aldrin epoxidation: P-450UT-A, P-450PB-C, P-450UT-H, P-450PB-B, P-450PCN-E, P-450UT-F, and P-450PB-D. P-450UT-I, P-450BNF-B, and P-450ISF-G were not very active at all. A novel aldrin metabolite, endo-dieldrin, was formed by cytochrome P-450UT-F in a 6-fold excess over dieldrin, which is the exo-isomer. The activity of aldrin epoxidase furthermore was assayed in liver microsomes from Sprague-Dawley rats of diverse physiological status and after pretreatment with various inducers resulting in a peculiar pattern of cytochrome P-450 isozymes. Untreated animals, at an age of 3 weeks, showed similar enzyme activities in both genders. During maturation, the activity of males increased by 3-fold, while the activity in females did not significantly change during this period. Pretreatment with pregnenolone-16-alpha-carbonitrile or dexamethasone strongly increased the activity in females. Pretreatment with dexamethasone did not increase the activity of males. A 50% depression of epoxidase activity was noted for males pretreated with 5,6-benzoflavone. Phenobarbital pretreatment increased the activity of females by 12-fold and of males by 2-fold. Males responded to pretreatment with polychlorinated biphenyls in a strain dependent fashion: enzyme activity was increased 2-fold in Sprague-Dawley rats but was not altered in Wistar rats. "Theoretical" values of microsomal epoxidase activity were calculated for weanling and adult Sprague-Dawley rats from turnover numbers and published data on the relative abundance of aldrin epoxidizing P-450 isozymes (Waxmann et al., Biochemistry 24, 4409, 1985). These values agreed with the activities determined. A similar statement can be made for male rats of both strains pretreated with inducers, when the ratio of enzyme activity of pretreated to control animals was used as a basis of comparison. The activity ratio of females pretreated with pregnenolone-16-alpha-carbonitrile, dexamethasone and phenobarbital, however, was much higher than the ratio calculated. Our results reveal that aldrin epoxidation is a reaction indicative of male specific and of phenobarbital-inducible cytochrome P-450 isozymes in rat liver.(ABSTRACT TRUNCATED AT 400 WORDS)
为探究哪些大鼠肝脏细胞色素P - 450种类参与艾氏剂环氧化反应，我们研究了从未经处理和经诱导剂处理的斯普拉格 - 道利大鼠中纯化得到的一系列细胞色素P - 450同工酶的催化活性。在所分析的十种细胞色素P - 450形式中，七种同工酶按活性递减顺序排列，催化了艾氏剂环氧化反应：P - 450UT - A、P - 450PB - C、P - 450UT - H、P - 450PB - B、P - 450PCN - E、P - 450UT - F和P - 450PB - D。P - 450UT - I、P - 450BNF - B和P - 450ISF - G几乎没有活性。一种新的艾氏剂代谢产物，内吸狄氏剂，由细胞色素P - 450UT - F形成，其生成量比外消旋异构体狄氏剂多6倍。此外，在来自不同生理状态的斯普拉格 - 道利大鼠的肝脏微粒体中，以及在用各种诱导剂预处理导致细胞色素P - 450同工酶出现特殊模式后，测定了艾氏剂环氧化酶的活性。未经处理的3周龄动物，雌雄两性的酶活性相似。在成熟过程中，雄性的活性增加了3倍，而在此期间雌性的活性没有显著变化。用孕烯醇酮 - 16 - α - 腈或地塞米松预处理可显著增加雌性的活性。用地塞米松预处理不会增加雄性的活性。用5,6 - 苯并黄酮预处理的雄性，其环氧化酶活性降低了50%。苯巴比妥预处理使雌性的活性增加了12倍，使雄性的活性增加了2倍。雄性对多氯联苯预处理的反应因品系而异：在斯普拉格 - 道利大鼠中酶活性增加了2倍，但在Wistar大鼠中没有改变。根据周转率以及已发表的关于艾氏剂环氧化P - 450同工酶相对丰度的数据（Waxmann等人，《生物化学》24, 4409, 1985），计算了断奶和成年斯普拉格 - 道利大鼠微粒体环氧化酶活性的“理论”值。这些值与测定的活性相符。当以预处理动物与对照动物的酶活性比值作为比较基础时，对于两种品系经诱导剂预处理的雄性大鼠也可得出类似结论。然而，用孕烯醇酮 - 16 - α - 腈、地塞米松和苯巴比妥预处理的雌性大鼠的活性比值远高于计算值。我们的结果表明，艾氏剂环氧化反应是一种反映大鼠肝脏中雄性特异性和苯巴比妥诱导性细胞色素P - 450同工酶的反应。（摘要截断于400字）
