Pyrimidine Ring-Opened Product from Oxidative DNA Damage of 5-Formyl-2'-deoxyuridine

After thymidine (dT) was treated with a Fenton-type reagent and further incubated for a long period (6 days) under physiological conditions (37 °C, pH 7.4), a new product, named dT*, was detected by HPLC in addition to the free thymine base and the known oxidative dT damage, 5-formyl-2'-deoxyuridine (f⁵dU). dT* was found to be formed from f⁵dU. The structure of dT* was determined to be 3-amino-2-carbamoyl-2-propenal-N³-2'-deoxyriboside, a pyrimidine ring-opened product from f⁵dU, on the basis of ¹H- and ¹³C NMR analyses and mass spectra. From the model compound 1-methyl-5-formyluracil, a similar ring-opened product was formed after the incubation. dT* was also detected in DNA treated with a Fenton-type reagent or γ-rays, followed by the prolonged incubation. dT* will be a new promising marker of oxidative DNA damage. The possible role of this product in oxy-radical-induced mutagenesis is discussed.