title: Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine.
abstract: 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.
authors.affiliation: School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Kelly
authors.forename: Gillian
authors.initials: G
authors.lastname: Whitaker
authors.forename: Blánaid
authors.initials: B
authors.lastname: White
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Smyth
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry*; D013058:Mass Spectrometry; D009532:Nickel / Q000633:toxicity*; D010084:Oxidation-Reduction
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D009532:Nickel; D004247:DNA