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Oxidative DNA damage induced by homogentisic acid, a tyrosine metabolite
Author(s) -
Hiraku Yusuke,
Yamasaki Masayoshi,
Kawanishi Shosuke
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00823-0
Subject(s) - dna damage , homogentisic acid , chemistry , dna , metabolite , catalase , biochemistry , thymine , autoxidation , tyrosine , oxidative phosphorylation , 8 hydroxy 2' deoxyguanosine , cytosine , guanine , peroxide , oxidative damage , deoxyguanosine , microbiology and biotechnology , dna oxidation , oxidative stress , biology , gene , nucleotide , organic chemistry
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 HGA 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.