Exocyclic
DNA adducts are considered as potential tools for the study of oxidative stress-related diseases, but an important aspect is their chemical reactivity towards
oxidant species. We report here the oxidation of 1-N2-etheno-2'-deoxyguanosine (1,N2-εdGuo) by singlet molecular
oxygen (1O2) generated by a non-ionic water-soluble endoperoxide [N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide (
DHPNO2)] and its corresponding
oxygen isotopically labeled [18O]-[N,N'-di(2,3-dihydroxypropyl)-1,4- naphthalenedipropanamide endoperoxide (DHPN18O2)], and by
photosensitization with two different
photosensitizers [
methylene blue (MB) and
Rose Bengal (RB)]. Products detection and characterization were achieved using high performance liquid chromatography (HPLC) coupled to ultraviolet and electrospray ionization (ESI) tandem mass spectrometry, and nuclear magnetic resonance (NMR) analyses. We found that dGuo is regenerated via reaction of 1O2 with the ε-linkage, and we propose a dioxetane as an intermediate, which cleaves and loses the
aldehyde groups as
formate residues, or alternatively, it generates a
1,2-ethanediol adduct. We also report herein the quenching rate constants of 1O2 by 1,N2-εdGuo and other etheno modified
nucleosides. The rate constant (kt) values obtained for etheno
nucleosides are comparable to the kt of dGuo. From these results, we suggest a possible role of 1O2 in the cleanup of etheno adducts by regenerating the normal base.