IMR Press / FBL / Volume 16 / Issue 3 / DOI: 10.2741/3739

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Mechanisms of oxidative DNA damage induced by carcinogenic arylamines
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1 Department of Environmental and Molecular Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan. mmurata@doc.medic.mie-u.ac.jp
2 Suzuka University of Medical Science, Faculty of Pharmaceutical Sciences, 3500-3, Suzuka, Mie, 513-8670, Japan
Academic Editor:King-Thom Chung
Front. Biosci. (Landmark Ed) 2011, 16(3), 1132–1143; https://doi.org/10.2741/3739
Published: 1 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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