Formation of 1,N6-ethenoadenine and 3,N4-ethenocytosine by lipid peroxidation products and nucleic acid bases

Chem Res Toxicol. 1995 Mar;8(2):278-83. doi: 10.1021/tx00044a013.


Lipid peroxidation (LPO) products are known to interact with DNA, yielding several types of adduct with nucleobases. In this study, we demonstrate the formation of two ethenobase adducts, 1,N6-ethenoadenine and 3,N4-ethenocytosine, by reaction of LPO products with nucleic acid bases. Rat liver microsomes were incubated at 37 degrees C for 30 min in the presence of inducers of LPO [Fe(II) or cumene hydroperoxide] and adenine or cytosine nucleotides or nucleosides, followed by further heating at 80 degrees C for 30 min to complete the reactions. The etheno adducts detected after immunoaffinity chromatography were 1,N6-etheno-cAMP and 1,N6-etheno-2'-deoxyadenosine (HPLC/fluorimetry), 3,N4-etheno-2'-deoxycytidine (competitive radioimmunoassay), and 1,N6-etheno-2'-deoxyadenosine 3'-monophosphate and 3,N4-etheno-2'-deoxycytidine 3'-monophosphate (32P-postlabeling). Incubation of arachidonic acid supplemented with Fe(II) also led to the formation of the 1,N6-etheno adduct from cAMP. LPO intermediates that may be involved are discussed. These data suggest that etheno adducts may be markers of DNA damage associated with LPO.

Publication types

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

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / biosynthesis
  • Adenine / isolation & purification
  • Animals
  • Arachidonic Acid / metabolism
  • Benzene Derivatives / metabolism
  • Chromatography, Affinity / methods
  • Cyclic AMP / biosynthesis
  • Cytosine / analogs & derivatives*
  • Cytosine / biosynthesis
  • Cytosine / isolation & purification
  • Iron / metabolism
  • Lipid Peroxidation*
  • Malondialdehyde / metabolism
  • Microsomes, Liver / metabolism
  • Mutagens*
  • Nucleic Acids / metabolism*
  • Rats


  • 3,N(4)-ethenocytosine
  • Benzene Derivatives
  • Mutagens
  • Nucleic Acids
  • 1,N(6)-ethenoadenine
  • Arachidonic Acid
  • Malondialdehyde
  • Cytosine
  • Cyclic AMP
  • Iron
  • Adenine
  • cumene hydroperoxide