4,5-Epoxy-2(E)-decenal-induced formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine adducts

Chem Res Toxicol. 2002 Mar;15(3):300-4. doi: 10.1021/tx010147j.


trans-4,5-Epoxy-2(E)-decenal reacted with 2'-deoxyadenosine to give 1,N(6)-etheno-2'-deoxyadenosine as well as other 2'-deoxyadenosine adducts. It also reacted with 2'-deoxyguanosine to give 1,N(2)-etheno-2'-deoxyguanosine and other 2'-deoxyguanosine adducts. Synthetic trans-4,5-epoxy-2(E)-decenal was quite stable under the reaction conditions that were used. It was not contaminated with 2,3-epoxyoctanal, a potential precursor to the formation of unsubstituted etheno adducts. Furthermore, using a sensitive LC/MS assay, it was possible to show that no 2,3-epoxyoctanal was formed during prolonged incubations of trans-4,5-epoxy-2(E)-decenal. Therefore, trans-4,5-epoxy-2(E)-decenal, a primary product of lipid peroxidation, is a precursor to the formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine. There is no need for an additional oxidation step such as would be required if trans,trans-2,4-decadienal or 4-hydroxy-2-nonenal were the lipid hydroperoxide decomposition products that initiated the formation of unsubstituted etheno adducts. These findings provide an important link between a primary product of lipid peroxidation and a mutagenic DNA lesion that has been detected in human tissues.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehydes / pharmacology*
  • Chromatography, Liquid
  • Deoxyadenosines / chemical synthesis*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemical synthesis*
  • Epoxy Compounds / pharmacology*
  • Hot Temperature
  • Lipid Peroxidation
  • Mass Spectrometry


  • 1,N(6)-etheno-2'-deoxyadenosine
  • 4,5-epoxy-2-decenal
  • Aldehydes
  • Deoxyadenosines
  • Epoxy Compounds
  • 1,N(2)-ethenodeoxyguanosine
  • Deoxyguanosine