Cross-link dimer formation of the acetaldehyde-derived cyclic 1,N 2-propano-2′-deoxyguanosine adduct using electrochemical oxidation

Abstract

The electrochemically oxidative lesion of the acetaldehyde-derived cyclic propano adduct 2 of 2′-deoxyguanosine 1 was identified as the cross-linked dimer 4 of adduct 2. Cross-link formation is explained by the nucleophilic preference of the exocyclic amino group in 2 to the carbocation 3 electrogenerated by 1-proton and 2-electron transfers. Dimer formation was also detected in duplex DNA during exposure to acetaldehyde followed by electrochemical oxidation. The dimer has been deduced to be an intrastrand cross-link generated specifically in the G-G sequence in duplex DNA, which is expected to contribute to acetaldehyde-mediated genotoxicity. © 2009 Pharmaceutical Society of Japan.