Oxidative damage to DNA constituents by iron-mediated fenton reactions. The deoxyguanosine family.

摘要: Damage by iron-mediated Fenton reactions under aerobic or anaerobic conditions to deoxycytidine, deoxycytidine-5′-monophosphate, d-CpC, d-CpCpC, and dCMP residues in DNA resulted at least 26 distinguishable products. Of these, 24 were identified high performance liquid chromatography retention times, radiolabeling, UV absorption spectra, chemical synthesis, fast atom bombardment mass spectrometry, resolution and/or NMR. The nature of the products was qualitatively similar for each substrate except d-CpC (and possibly d-CpCpC) which 5-hydroxy-deoxycytidine uniquely present 1-carbamoyl-1-carboxy-4-(2-deoxy-β—erythropentofuranosyl)glycinamide absent. dC, d-CpCpC but not largely quenched ethanol, indicating that iron is strongly associated only with DNA. presence oxygen had little effect dC quantitative qualitative effects a significantly NADH could drive reaction cause damage family vitro, consistent previous proposal reducing agent vivo (Imlay, J.A., Linn, S. (1988) Science 240, 1302-1309). Finally, spectrum compared ionizing radiation mechanisms leading formation are proposed.