Oxidative DNA damage induced by homogentisic acid, a tyrosine metabolite

被引：24

作者：

Hiraku, Y ^{[1
]}

Yamasaki, M ^{[1
]}

Kawanishi, S ^{[1
]}

机构：

[1] Mie Univ, Sch Med, Dept Hyg, Tsu, Mie 5148507, Japan

来源：

FEBS LETTERS | 1998年 / 432卷 / 1-2期

关键词：

homogentisic acid; tyrosine metabolite; DNA damage; active oxygen species; hydrogen peroxide; copper;

D O I：

10.1016/S0014-5793(98)00823-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We examined the mechanism of DNA damage induced by a mutagenic tyrosine metabolite, homogentisic acid (HGA), using (32)P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor gene. HGA caused DNA damage in the presence of Cu(II), particularly at thymine and cytosine residues. Catalase and bathocuproine inhibited the DNA damage, suggesting the involvement of H(2)O(2) and Cu(I), The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by I-IGA increased depending on HGA concentration in the presence of Cu(II), It is concluded that H(2)O(2) is generated during Cu(II)-catalyzed HGA autoxidation and reacts with Cu(I) to form the Cu(I)-peroxide complex, capable of causing oxidative DNA damage, (C) 1998 Federation of European Biochemical Societies.

引用

页码：13 / 16

页数：4

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