Friedman F K, Wiebel F J, Gelboin H V
Pharmacology. 1985;31(4):194-202. doi: 10.1159/000138115.
The microsomal cytochrome P-450-dependent aryl hydrocarbon hydroxylase is important in the detoxification of polycyclic hydrocarbons as well as their activation to cytotoxic or carcinogenic derivatives. We have studied compounds that can modify the activity of this enzyme system. Three types of flavones are distinguished on the basis of their effect on the constitutive and polycyclic hydrocarbon-induced rat hepatic enzyme activity: (a) the 5,6- and 7,8-benzoflavones and their more hydrophobic derivatives inhibit the induced enzyme and increase or do not affect the constitutive enzyme activity; (b) derivatives typified by the 4'-hydroxylated benzoflavones similarly decrease both induced and constitutive activities; (c) polyhydroxyflavones inhibit the constitutive enzyme more than the induced enzyme. Two polycyclic hydrocarbons, 9-chloro-7H-dibenzo(a,g)carbazole and 6-aminochrysene, both potent inhibitors of the enzyme system, affect the constitutive and induced enzyme similar to compounds in groups a and b, respectively. The various activity-modulating compounds are useful reagents for distinguishing closely related enzymes present in a variety of different tissues and species under different conditions.
微粒体细胞色素P - 450依赖性芳烃羟化酶在多环烃的解毒以及将其激活为细胞毒性或致癌衍生物方面起着重要作用。我们研究了能够改变该酶系统活性的化合物。根据它们对组成型和多环烃诱导的大鼠肝酶活性的影响，区分出三种类型的黄酮：(a) 5,6 - 和7,8 - 苯并黄酮及其疏水性更强的衍生物抑制诱导酶，并增加或不影响组成型酶活性；(b) 以4'-羟基化苯并黄酮为代表的衍生物同样降低诱导活性和组成型活性；(c) 多羟基黄酮对组成型酶的抑制作用比对诱导酶的抑制作用更强。两种多环烃，9 - 氯 - 7H - 二苯并(a,g)咔唑和6 - 氨基 Chrysene，都是该酶系统的有效抑制剂，它们分别对组成型酶和诱导酶的影响类似于a组和b组中的化合物。各种活性调节化合物是用于区分在不同条件下存在于多种不同组织和物种中的密切相关酶的有用试剂。
