Novel 1,N-6-etheno-2 '-deoxyadenosine adducts from lipid peroxidation products

trans,trans-2,4-Decadienal (DDE) is a widespread alpha,beta-unsaturated ald ehyde found, for example, in food, water, and environmental pollutants. DDE is also endogenously generated as a breakdown product of lipid peroxidatio n in cell membranes. In the work presented here, the reaction of DDE with 2 '-deoxyadenosine (dAdo) was investigated in an effort to assess its possibl e DNA damage potential. Besides 1,N-6-etheno-2'-deoxyadenosine and two prod ucts, namely, 1-[3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[2,1-i ]purin-7-yl]-1,2,3-octanetriol (adduct I) and 1-[3-(2-deoxy-beta-D-erythro- pentofuranosyl)-3H-imidazo[2,1-i]purin-7-yl]-1,2-heptanediol (adduct II), p reviously described by our group, two novel etheno adducts were identified. Thus, 1-[3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3h-imidazo[2.1-i]purin- 7-yl]-1-hexanol (adduct III) and 1-[3-(2-deoxy-beta-D-erythro-pentofuranosy l)-3H-imidazo[2,1-i]purin-7-yl]-2,3-epoxy-1-octanol (adduct IV) were isolat ed by reverse-phase high-performance liquid chromatography and characterize d on the basis of extensive spectroscopic measurements. The formation of th e adducts is likely to involve initial DDE oxidation followed by generation of reactive intermediates such as diepoxides, epoxides, and/or hydroperoxi des. The subsequent reaction of the latter oxidation products with dAdo wil l give rise to the four described adducts. We also demonstrated here that u pon oxidation, DDE reacts with calf thymus DNA, producing the four dAdo add ucts. Interestingly, two of them are the expected products arising from the reaction of dAdo with 4-hydroxy-trans-2-nonenal (HNE) and trans-2-octenal, two other important breakdown lipid peroxidation products. The reactivity of DDE with DNA is lower than that of the latter aldehydes. However, DDE pr oduced a wider variety of adducts. The characterization of the different DN A-etheno adducts and the determination of the mechanism of formation are of great importance for a better understanding of the deleterious biological effects associated with this class of compounds.