Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine oxidation

Mol Biosyst. 2005 Dec;1(5-6):373-81. doi: 10.1039/b511756a. Epub 2005 Oct 25.

Abstract

8-Oxo-7,8-dihydroguanine (8-oxoGua), an important biomarker of DNA damage in oxidatively generated stress, is highly reactive towards further oxidation. Much work has been carried out to investigate the oxidation products of 8-oxoGua by one-electron oxidants, singlet oxygen, and peroxynitrite. This report details for the first time, the iron- and copper-mediated Fenton oxidation of 8-oxoGua and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Oxidised guanidinohydantoin (Gh(ox)) was detected as the major product of oxidation of 8-oxoGua with iron or copper and hydrogen peroxide, both at pH 7 and pH 11. Oxaluric acid was identified as a final product of 8-oxoGua oxidation. 8-oxodGuo was subjected to oxidation under the same conditions as 8-oxoGua. However, dGh(ox) was not generated. Instead, spiroiminodihydantoin (Sp) was detected as the major product for both iron and copper mediated oxidation at pH 7. It was proposed that the oxidation of 8-oxoGua was initiated by its one-electron oxidation by the metal species, which leads to the reactive intermediate 8-oxoGua (+), which readily undergoes further oxidation. The product of 8-oxoGua and 8-oxodGuo oxidation was determined by the 2'-deoxyribose moiety of the 8-oxodGuo, not whether copper or iron was the metal involved in the oxidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Copper / chemistry
  • Deoxyguanosine / chemistry*
  • Guanidines / chemistry*
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry
  • Hydantoins / chemistry*
  • Models, Molecular
  • Oxidation-Reduction
  • Spiro Compounds / chemistry*

Substances

  • Guanidines
  • Hydantoins
  • Spiro Compounds
  • guanidinohydantoin
  • spiroiminodihydantoin
  • Guanosine
  • Guanine
  • Copper
  • Deoxyguanosine