Murakami Hiroya, Esaka Yukihiro, Uno Bunji
Gifu Pharmaceutical University, Mitahora-higashi, Japan.
Chem Pharm Bull (Tokyo). 2009 Dec;57(12):1434-6. doi: 10.1248/cpb.57.1434.
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.
乙醛衍生的2'-脱氧鸟苷1的环状丙烷加合物2的电化学氧化损伤被鉴定为加合物2的交联二聚体4。交联的形成可以通过加合物2中环外氨基对由1-质子和2-电子转移产生的碳正离子3的亲核偏好来解释。在暴露于乙醛后进行电化学氧化的双链DNA中也检测到了二聚体的形成。已推断该二聚体是双链DNA中G-G序列特异性产生的链内交联，预计这会导致乙醛介导的遗传毒性。
