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

Chem Res Toxicol. 2019 Apr 15;32(4):737-744. doi: 10.1021/acs.chemrestox.8b00401. Epub 2019 Feb 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • DNA / analysis
  • DNA / metabolism*
  • DNA Damage
  • Deoxyuridine / analogs & derivatives*
  • Deoxyuridine / chemistry
  • Deoxyuridine / metabolism
  • Molecular Structure
  • Oxidation-Reduction
  • Pyrimidines / chemistry
  • Pyrimidines / metabolism*

Substances

  • Pyrimidines
  • 5-formyl-2'-deoxyuridine
  • DNA
  • calf thymus DNA
  • pyrimidine
  • Deoxyuridine