Interspecies differences in metabolism of heterocyclic aromatic amines by rat and human P450 1A2

被引：44

作者：

Turesky, RJ

Constable, A

Fay, LB

Guengerich, FP

机构：

[1] Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland

[2] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA

来源：

CANCER LETTERS | 1999年 / 143卷 / 02期

关键词：

hetercyclic aromatic amines (HAAs); food carcinogens; cytochrome P450; N-oxidation; interspecies comparisons;

D O I：

10.1016/S0304-3835(99)00137-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The catalytic efficiences of cytochrome P450 (P450)-mediated N-oxidation of the 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by recombinant human P450 1A2 were 10-19-fold higher than rat P450 1A2, while methoxyresorufin O-demethylation activity was comparable for both P450s. Similar findings were observed with rat and human liver microsomal samples. Interspecies differences in P450 enzyme expression and catalytic activities may be significant and must be considered when assessing human health risk. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：109 / 112

页数：4

共 11 条

[1]

BOOBIS AR, 1995, P 23 INT S PRINC TAK, P134

[2] HUMAN CYTOCHROME P-450PA (P-450IA2), THE PHENACETIN O-DEETHYLASE, IS PRIMARILY RESPONSIBLE FOR THE HEPATIC 3-DEMETHYLATION OF CAFFEINE AND N-OXIDATION OF CARCINOGENIC ARYLAMINES - (AROMATIC-AMINES HETEROCYCLIC AMINES CARCINOGEN METABOLISM) [J].