Effect of nucleotide substitutions in N-acetyltransferase-1 on N-acetylation (deactivation) and O-acetylation (activation) of arylamine carcinogens:: implications for cancer predisposition

被引：30

作者：

Fretland, AJ ^{[1
]}

Doll, MA ^{[1
]}

Zhu, YQ ^{[1
]}

Smith, L ^{[1
]}

Leff, MA ^{[1
]}

Hein, DW ^{[1
]}

机构：

[1] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA

来源：

CANCER DETECTION AND PREVENTION | 2002年 / 26卷 / 01期

关键词：

N-acetyltransferase-1; acetylation polymorphism; single nucleotide polymorphism; recombinant expression;

D O I：

10.1016/S0361-090X(02)00005-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genetic polymorphism in N-acetyltransferase-1 (NAT1) is associated with increased risk of various cancers, but epidemiological investigations are compromised by poor understanding of the relationship between NAT1 genotype and phenotype. Human reference NAT1*4 and 12 known human NAT1 allelic variants possessing nucleotide polymorphisms in the NAT1 coding region were cloned and expressed in yeast (Schizosaccharomyces pombe). Large reductions in the N-acetylation of 4-aminobiphenyl and the O-acetylation of N-hydroxy-2-aminofluorene were observed for recombinant NAT1 allozymes encoded by NAT1*14B, NAT1* 15, NAT1*17, NAT1*19, and NAT1*22. Each of these alleles exhibited substantially lower expression of NAT1 protein than the reference NAT1*4 and the other NAT1 alleles. These results show an important effect of the NAT1 genetic polymorphism on the N- and O-acetylation of arylamine carcinogens, suggesting modification of cancer susceptibility following exposures to arylamine carcinogens. (C) 2002 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved.

引用

页码：10 / 14

页数：5

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