Oxidative DNA damage induced by homogentisic acid, a tyrosine metabolite

FEBS Letters

Kawanishi, Shosuke¹  Yamasaki, Masayoshi¹  Hiraku, Yusuke¹ 

[1] Department of Hygiene, Mie University School of Medicine, Tsu, Mie 514-8507, Japan

关键词: Homogentisic acid;    Tyrosine metabolite;    DNA damage;    Active oxygen species;    Hydrogen peroxide;    Copper;    HGA;    homogentisic acid;    8-oxodG;    8-oxo-7;    8-dihydro-2′-deoxyguanosine;    HPLC;    high performance liquid chromatography;    HPLC-ECD;    electrochemical detector coupled to HPLC;    DTPA;    diethylenetriamine N;    N;    N′;    N″;    N″-pentaacetic acid;    SOD;    superoxide dismutase;   

DOI  :  10.1016/S0014-5793(98)00823-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We examined the mechanism of DNA damage induced by a mutagenic tyrosine metabolite, homogentisic acid (HGA), using ³²P-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 H₂O₂ and Cu(I). The formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine by HGA increased depending on HGA concentration in the presence of Cu(II). It is concluded that H₂O₂ 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.

【 授权许可】

Unknown