Oxidative DNA damage induced by homogentisic acid, a tyrosine metabolite

Abstract

We examined the mechanism of DNA damage induced by a mutagenic tyrosine metabolite, homogentisic acid (HGA), using QP P-5P-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 P O P and Cu(I). The formation of 8-oxo-7,8-dihydro-2P-deoxyguanosine by HGA increased depending on HGA concentration in the presence of Cu(II). It is concluded that H P O P 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.z 1998 Federation of European Biochemical Societies.

Characterization of melanin-overproducing transposon mutants ofPseudomonas putidaF6

“…It is possible that the production of a HGA‐based polymer in the growth medium by mutant F6‐HDO allows greater resistance to H 2 O 2 . HGA auto‐oxidizes at pH 7 yielding superoxide (O 2 •− ) and H 2 O 2 (Martin & Batkoff, 1989; Hiraky et al , 1998). Both of these are highly reactive oxygen species that are able to cause severe cell damage.…”

Antioxidant profile of strawberry tree honey and its marker homogentisic acid in several models of oxidative stress

“…HGA has been reported to induce cytotoxic and mutagenic 0308-8146/$ -see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.foodchem.2011.05.072 effects and it appears to occur through an oxidative mechanism based on the ability of this compound to undergo autoxidation, leading to quinone formation with the production of reactive oxygen species (Hiraku, Yamasaki, & Kawanishi, 1998;Urios et al, 2003). The accumulation of HGA in connective tissues, the formation of its oxidised/polymerised products and oxygen radical generation have been implicated in aetiology of ochronosis, inflammation and tissue degeneration observed in patients with alkaptonuria, a rare genetic disease associated with deficient homogentisate 1,2-dioxygenase activity in the liver (Braconi et al, 2010;Phornphutkul et al, 2002).…”

A Rare Case of Acquired Methemoglobinemia Associated with Alkaptonuria

“…During the autoxidation of HGA, superoxide anion (O2 -) is generated via a reaction with oxygen, thus resulting in the production of hydrogen peroxide (H2O2). Subsequently, H2O2 oxidizes oxyhemoglobin to methemoglobin (7,8). In the current case, during hospitalization, the patient exhibited renal dysfunction, which was thought to be a side effect of antibiotic therapy, and her urinary output decreased.…”