title: Formation of 1,N6-ethenoadenine and 3,N4-ethenocytosine by lipid peroxidation products and nucleic acid bases.
abstract: 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.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: el Ghissassi
authors.forename: A
authors.initials: A
authors.lastname: Barbin
authors.forename: J
authors.initials: J
authors.lastname: Nair
authors.forename: H
authors.initials: H
authors.lastname: Bartsch
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001555:Benzene Derivatives / Q000378:metabolism; D002846:Chromatography, Affinity / Q000379:methods; D000242:Cyclic AMP / Q000096:biosynthesis; D003596:Cytosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D009696:Nucleic Acids / Q000378:metabolism*; D051381:Rats
chemical_list: C018289:3,N(4)-ethenocytosine; D001555:Benzene Derivatives; D009153:Mutagens; D009696:Nucleic Acids; C004981:1,N(6)-ethenoadenine; D016718:Arachidonic Acid; D008315:Malondialdehyde; D003596:Cytosine; D000242:Cyclic AMP; D007501:Iron; D000225:Adenine; C007164:cumene hydroperoxide