Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine
Kelly, Michele C. and Whitaker, Gillian and White, Blánaid and Smyth, Malcolm R. (2007) Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine. Free Radical Biology and Medicine, 42 (11). pp. 1680-1689. ISSN 0891-5849
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Oxidative DNA damage is one of the most important and most studied mechanisms of disease. It has been associated with a range of terminal diseases such as cancer, heart disease, hepatitis, and HIV, as well as with a variety of everyday ailments. There are various mechanisms by which this type of DNA damage can be initiated, through radiation and chemical oxidation, among others; however, these mechanisms have yet to be fully elucidated. A HPLC-UV-EC study of the oxidation of DNA mediated by nickel(II) obtained results that show an erratic, almost oscillatory formation of 8-oxoguanine (8-oxoG) from free guanine and from guanine in DNA. Sporadic 8-oxoG concentrations were also observed when 8-oxoG alone was subjected to these conditions. A HPLC-MS/MS study showed the formation of oxidised-guanidinohydantoin (oxGH) from free guanine at pH 11, and the formation of guanidinohydantoin (GH) from DNA at pH 5.5.
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