Novel 1,N(6)-etheno-2'-deoxyadenosine adducts from lipid peroxidation products.
trans,trans-2,4-Decadienal (DDE) is a widespread alpha, beta-unsaturated aldehyde found, for example, in food, water, and environmental pollutants. DDE is also endogenously generated as a breakdown product of lipid peroxidation in cell membranes. In the work presented here, the reaction of DDE with 2'-deoxyadenosine (dAdo) was investigated in an effort to assess its possible DNA damage potential. Besides 1,N(6)-etheno-2'-deoxyadenosine and two products, 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), previously 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-pentofuranosyl)-3H-imidazo[2, 1-i]purin-7-yl]-2,3-epoxy-1-octanol (adduct IV) were isolated by reverse-phase high-performance liquid chromatography and characterized on the basis of extensive spectroscopic measurements. The formation of the adducts is likely to involve initial DDE oxidation followed by generation of reactive intermediates such as diepoxides, epoxides, and/or hydroperoxides. The subsequent reaction of the latter oxidation products with dAdo will give rise to the four described adducts. We also demonstrated here that upon oxidation, DDE reacts with calf thymus DNA, producing the four dAdo adducts. 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 produced a wider variety of adducts. The characterization of the different DNA-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.
Carvalho
V M
VM
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26.077, CEP 05513-970, São Paulo, Brazil.
Asahara
F
F
Di Mascio
P
P
de Arruda Campos
I P
IP
Cadet
J
J
Medeiros
M H
MH
D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D004787:Environmental Pollution / Q000032:analysis; D015227:Lipid Peroxidation; D013058:Mass Spectrometry; D015394:Molecular Structure
D000447:Aldehydes; D018736:DNA Adducts; D003839:Deoxyadenosines; C057349:2,4-decadienal; D004247:DNA