4.7 Article

Mechanism of DNA damage induced by bromate differs from general types of oxidative stress

Journal

TOXICOLOGY
Volume 221, Issue 2-3, Pages 172-178

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2006.01.002

Keywords

potassium bromate; glutathione; cysteine; 8-oxo-7,8-dihydro-2 '-deoxyguanosine

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A representative reactive oxygen species (ROS), hydroxyl radical ((OH)-O-center dot), is a highly reactive species and induces DNA backbone breakage. (OH)-O-center dot also oxidizes every DNA base. The interaction of (OH)-O-center dot with guanine leads to the generation of not only piperidine-resistant 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) but also various piperidine-labile products. On the other hand, potassium bromate (KBrO3) induces specific formation of 8-oxodG in the presence of SH compounds, such as glutathione (GSH) and cysteine (Cys). GSH/Cys reduces KBrO3 (BrO3-) to BrO2, which abstracts one electron from guanine. The one-electron oxidation of guanine may yield cation radicals followed by the reaction with a water molecule, leading to 8-oxodG formation. Therefore, mechanism of bromate-induced oxidative DNA damage is different from general types of oxidative stress such as (OH)-O-center dot. (c) 2006 Aww Research Foundation. Published by Elsevier Ireland Ltd. All rights reserved.

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