The abilities of selenium dioxide and selenite ion to coordinate DNA-bound metal ions and decrease oxidative DNA damage

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• 作者：William E. Hart^a ; Steven P. Marczak^b ; Andrew R. Kneller^c ; Robert A. French^a ; Daniel L. Morris Jr.^a ; ^{morris@rose-hulman.edu}
• 关键词：Oxidative DNA damage ; 8-hydroxy-2&prime ; -deoxyguanosine ; Inorganic selenium compounds ; Antioxidant
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：125
• 期：Complete
• 页码：1-8
• 全文大小：779 K

文摘

Several transition metals react with H₂O₂ and produce reactive oxygen species (ROS) responsible for oxidative damage linked to many diseases and disorders, and species that form coordination complexes with these metal ions show promise as antioxidants. The present study demonstrates that metal-mediated radical and non-radical oxidative DNA damage decreases when selenium dioxide (SeO₂) and sodium selenite (Na₂SeO₃) are present. Radical-induced damage is associated with production of 8-hydroxy-2¡ä-deoxyguanosine (8-OH-dG), which arises from ROS generated at or near the guanine base, and the selenium compounds reduce Fe(II)-, Cr(III)- and Cu(II)-mediated radical damage to differing degrees based on the identity of the metal ion and the order in which the metals, selenium compounds and DNA are combined. Radical damage arising from Fe(II) and Cr(III) decreases substantially when they are pre-incubated with the selenium compounds prior to adding DNA. Non-radical damage is associated with oxidation of the adenine base in the presence of high H₂O₂ concentrations through an ionic mechanism, and this type of damage also decreases significantly when the selenium compounds are allowed to interact with the metal ions before adding DNA. Fluorescence studies using dihydrodichlorofluorescein diacetate (DCF-DA) to probe ROS formation indicate that the majority of the SeO₂- and SeO₃^2 ?-metal systems in combination with H₂O₂ (no DNA present) produce ROS to the same degree as the metal/H₂O₂ systems in the absence of the selenium compounds, suggesting that selenium-metal complexes react with H₂O₂ in a sacrificial manner that protects DNA from oxidative damage.