Open Access
Article
Mechanisms of oxidative DNA damage induced by carcinogenic arylamines
Mariko Murata1,Shosuke Kawanishi1
1
Department of Environmental and Molecular Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan. mmurata@doc.medic.mie-u.ac.jp
DOI: 10.2741/3739 Volume 16 Issue 3, pp.1132-1143
Published: 01 January 2011
(This article belongs to the Special Issue Arylamine induced carcinogenesis)
Abstract

Most arylamines are pro-carcinogens, and require metabolic activation to yield ultimate carcinogen metabolites. O-Acetylation of the N-hydroxy form of an arylamine yields an acetoxyarylamine, which can form a highly reactive arylnitrenium ion, the ultimate metabolite responsible for DNA adduct formation. However, we demonstrate here that the N-hydroxy and nitroso forms of arylamines can also induce DNA damage, including 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) lesions, via reactive oxygen species formation. The N-hydroxy and nitroso derivatives of carcinogenic arylamines may contribute to the carcinogenic process through H2O2 formation. N-Hydroxy derivatives induce metal-mediated DNA damage, with remarkable enhancement by NADH. Nitroso derivatives induce NADH-dependent DNA damage in the presence of metal ions. Hydroxy derivatives of arylamines formed by enzymatic hydroxylation or as o- or p-aminophenols can also induce DNA damage in the presence of metal ions. The autoxidation of o-phenylenediamine and several arylamine metabolites is accelerated in the presence of SOD or manganese, resulting in the enhancement of metal-mediated DNA damage. The oxidative DNA damage induced by arylamine compounds may participate in chemical carcinogenesis, in addition to DNA adduct formation.

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Mariko Murata, Shosuke Kawanishi. Mechanisms of oxidative DNA damage induced by carcinogenic arylamines. Frontiers in Bioscience-Landmark. 2011. 16(3); 1132-1143.