4,5-Epoxy-2(E)-decenal-induced formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine adducts.
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.
Lee
Seon Hwa
SH
Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
Oe
Tomoyuki
T
Blair
Ian A
IA
D000447:Aldehydes / Q000494:pharmacology*; D002853:Chromatography, Liquid; D003839:Deoxyadenosines / Q000138:chemical synthesis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004852:Epoxy Compounds / Q000494:pharmacology*; D006358:Hot Temperature; D015227:Lipid Peroxidation; D013058:Mass Spectrometry
C115182:1,N(6)-etheno-2'-deoxyadenosine; C096140:4,5-epoxy-2-decenal; D000447:Aldehydes; D003839:Deoxyadenosines; D004852:Epoxy Compounds; C054579:1,N(2)-ethenodeoxyguanosine; D003849:Deoxyguanosine