FORMATION OF 1,N-6-ETHENO-2'-DEOXYADENOSINE ADDUCTS BY TRANS,TRANS-2,4-DECADIENAL

trans,trans-2,4-Decadienal (DDE) is an important breakdown product of lipid peroxidation. This aldehyde is cytotoxic to mammalian cells and is known to be implicated in DNA damage. Therefore, attempts were made in this work to assess the reactivity of DDE with 2'-deoxyadenosine ( dAdo). It was shown that DDE is able to bind to 2'-deoxyadenosine, yie lding highly fluorescent products. Besides 1,N-6-etheno-2'-deoxyadenos ine (epsilon dAdo), two other related adducts, syl)3H-imidazo[2,1-i]pu rin-7-yl]-1,2,3-octanetriol and syl)-3H-imidazo[2,1-i]purin-7-yl]-1,2- heptanediol, were isolated by reverse phase high-performance liquid ch romatography and characterized on the basis of their UV, fluorescence, nuclear magnetic resonance, and mass spectrometry features. The react ion mechanism for the formation of the DDE-2'-deoxyadenosine adducts i nvolves 2,4-decadienal epoxidation and subsequent addition to the N-2 amino group of 2'-deoxyadenosine, followed by cyclization at the N-1 s ite. Adducts differ by the length of carbon side chain and the number of hydroxyl groups. The present data indicate that DDE can be epoxidiz ed by peroxides, and the resulting products are able to form several a dducts with 2'-deoxyadenosine and/or DNA. Endogenous DNA adduct format ion can contribute to the already reported high cytotoxicity of DDE to mammalian cells.