N-ACETYLATION AND O-ACETYLATION OF AROMATIC AND HETEROCYCLIC AMINE CARCINOGENS BY HUMAN MONOMORPHIC AND POLYMORPHIC ACETYLTRANSFERASES EXPRESSED IN COS-1 CELLS
N-ACETYLATION AND O-ACETYLATION OF AROMATIC AND HETEROCYCLIC AMINE CARCINOGENS BY HUMAN MONOMORPHIC AND POLYMORPHIC ACETYLTRANSFERASES EXPRESSED IN COS-1 CELLS
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DOI：
10.1016/0006-291x(92)91703-s
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发表时间：
1992-06-30
影响因子：
3.1
通讯作者：
KADLUBAR, FF
中科院分区：
文献类型：
--
作者：
MINCHIN, RF;REEVES, PT;KADLUBAR, FF
在猴肾COS-1细胞中表达了人单态和多态芳香胺乙酰转移酶（EC 2.3.1.5），并用于研究一些致癌胺及其N-羟基代谢产物的N-和O-乙酰化。单态酶能将芳香胺、2-氨基芴和4-氨基联苯N-乙酰化，也能将它们的N-羟基衍生物O-乙酰化。食物来源的杂环胺（Glu-P-1，PhIP，IQ，MeIQx）都不是底物，它们的N-羟基代谢产物很少被该同工酶O-乙酰化。相比之下，多晶型乙酰转移酶催化两种芳香胺的N-乙酰化，并在较小程度上，Glu-P-1和PhIP。然而，所有六个N-羟基胺底物容易O-乙酰化，形成DNA结合的加合物的多态性同工酶。这些数据表明，对于杂环胺致癌物，快速乙酰化的个体将容易受到其遗传毒性的影响。
Human monomorphic and polymorphic arylamine acetyltransferases (EC 2.3.1.5) were expressed in monkey kidneyCOS-1 cells and used to study theN- andO-acetylation of a number of carcinogenic amines and theirN-hydroxy metabolites. The monomorphic enzymeN-acetylated the aromatic amines, 2-aminofluorene and 4-aminobiphenyl, and alsoO-acetylated theirN-hydroxy derivatives. None of the food-derived heterocyclic amines (Glu-P-1, PhIP, IQ, MeIQx) were substrates and theirN-hydroxy metabolites were poorlyO-acetylated by this isozyme. By contrast, the polymorphic acetyltransferase catalyzed theN-acetylation of both aromatic amines, and to a lesser extent, Glu-P-1 and PhIP. However, all sixN-hydroxy amine substrates were readilyO-acetylated to form DNA-bound adducts by the polymorphic isozyme. These data suggest that, for the heterocyclic amine carcinogens, rapid acetylator individuals will be predisposed to their genotoxicity.