METABOLISM OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK), A TOBACCO-SPECIFIC CARCINOGEN, BY RABBIT NASAL MICROSOMES AND CYTOCHROME-P450S NMA AND NMB

被引：40

作者：

HONG, JY ^{[1
]}

DING, XX ^{[1
]}

SMITH, TJ ^{[1
]}

COON, MJ ^{[1
]}

YANG, CS ^{[1
]}

机构：

[1] UNIV MICHIGAN,DEPT BIOL CHEM,ANN ARBOR,MI 48109

来源：

CARCINOGENESIS | 1992年 / 13卷 / 11期

关键词：

D O I：

10.1093/carcin/13.11.2141

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Rabbit nasal olfactory and respiratory microsomes were found to catalyze the alpha-hydroxylation of 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK) with specific activities of 262 and 136 pmol/min/mg protein in the formation of keto aldehyde, and of 318 and 190 pmol/min/mg protein in the formation of keto alcohol respectively. The formation of N.NK-N-oxide was observed in experiments with rabbit olfactory and respiratory microsomes, but not with rat nasal microsomes. However, the rat nasal microsomes had higher activity in catalyzing the alpha-hydroxylation of NNK. In a reconstituted system, rabbit P450NMa, a major constitutive P450 isozyme in nasal microsomes, displayed high activities in the formation of the keto aldehyde and the keto alcohol with apparent K(m) values of 15 and 9 muM respectively. In comparison, rabbit olfactory specific P450NMb had a low activity in catalyzing the formation of keto aldehyde (K(m) = 186 muM) and no activity in the formation of keto alcohol. The P450NMa-catalyzed oxidation of NNK was inhibited by nicotine and diallyl sulfide. Kinetic studies indicated that nicotine is a competitive inhibitor. These results demonstrate that enzymes in rabbit nasal microsomes, especially P450NMa, efficiently catalyze the bioactivation of NNK.

引用

页码：2141 / 2144

页数：4

共 20 条

[1] TOXIC AND CARCINOGENIC AGENTS IN UNDILUTED MAINSTREAM SMOKE AND SIDESTREAM SMOKE OF DIFFERENT TYPES OF CIGARETTES [J].