N-NITROSODIALKYLAMINE DEALKYLATION IN RECONSTITUTED SYSTEMS CONTAINING CYTOCHROME-P-450 PURIFIED FROM PHENOBARBITAL-NAPHTHOFLAVONE-TREATED AND BETA-NAPHTHOFLAVONE-TREATED RATS

被引：17

作者：

KAWANISHI, T ^{[1
]}

OHNO, Y ^{[1
]}

TAKANAKA, A ^{[1
]}

KAWANO, S ^{[1
]}

YAMAZOE, Y ^{[1
]}

KATO, R ^{[1
]}

OMORI, Y ^{[1
]}

机构：

[1] KEIO UNIV,SCH MED,DEPT PHARMACOL,TOKYO 160,JAPAN

来源：

ARCHIVES OF TOXICOLOGY | 1992年 / 66卷 / 02期

关键词：

N-NITROSAMINE; CYTOCHROME-P-450; RAT; PHENOBARBITAL; BETA-NAPHTHOFLAVONE;

D O I：

10.1007/BF02342508

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or beta-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIBI) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.

引用

页码：137 / 142

页数：6

共 33 条

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