A pyrimidine ring-opened product from the oxidative DNA damage 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 the mass spectrum. 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 gamma-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.