Kawanishi Shosuke, Murata Mariko
Department of Environmental and Molecular Medicine, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan.
Toxicology. 2006 Apr 17;221(2-3):172-8. doi: 10.1016/j.tox.2006.01.002. Epub 2006 Feb 2.
A representative reactive oxygen species (ROS), hydroxyl radical (*OH), is a highly reactive species and induces DNA backbone breakage. *OH also oxidizes every DNA base. The interaction of *OH 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.
一种具有代表性的活性氧（ROS），即羟基自由基（*OH），是一种高活性物质，可导致DNA主链断裂。*OH还会氧化每个DNA碱基。OH与鸟嘌呤的相互作用不仅会产生抗哌啶的8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代脱氧鸟苷，8-oxodG），还会产生各种对哌啶敏感的产物。另一方面，溴酸钾（KBrO3）在存在谷胱甘肽（GSH）和半胱氨酸（Cys）等硫氢化合物的情况下会诱导8-氧代脱氧鸟苷的特异性形成。GSH/Cys将KBrO3（BrO3-）还原为BrO2，BrO2从鸟嘌呤中夺取一个电子。鸟嘌呤的单电子氧化可能会产生阳离子自由基，随后与水分子反应，导致8-氧代脱氧鸟苷的形成。因此，溴酸盐诱导的氧化性DNA损伤机制与OH等一般类型的氧化应激不同。
