OXIDATIVE DNA-DAMAGE INDUCED BY HOMOGENTISIC ACID, A TYROSINE METABOLITE

We examined the mechanism of DNA damage induced by a mutagenic tyrosin e metabolite, homogentisic acid (HGA), using P-32-5'-end-labeled DNA f ragments obtained from the human p53 tumor suppressor gene. HGA caused DNA damage in the presence of Cu(II), particularly at thymine and cyt osine residues. Catalase and bathocuproine inhibited the DNA damage, s uggesting the involvement of H2O2 and Cu(I), The formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine by I-IGA increased depending on HGA concen tration in the presence of Cu(II), It is concluded that H2O2 is genera ted during Cu(II)-catalyzed HGA autoxidation and reacts with Cu(I) to form the Cu(I)-peroxide complex, capable of causing oxidative DNA dama ge, (C) 1998 Federation of European Biochemical Societies.