4,5-Epoxy-2(E)-decenal-induced formation of 1,N6-etheno-2′-deoxyadenosine and 1,N2-etheno-2′-deoxyguanosine adducts

Abstract

Trans-4,5-Epoxy-2(E)-decenal reacted with 2′-deoxyadenosine to give 1,N6-etheno-2′-deoxyadenosine as well as other 2′-deoxyadenosine adducts. It also reacted with 2′-deoxyguanosine to give 1,N2-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,N6-etheno-2′-deoxyadenosine and 1,N2-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.