Formation of 1,N6-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, yielding highly fluorescent products. Besides 1, N6-etheno-2'-deoxyadenosine (epsilondAdo), two other related adducts, 1-[3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[2, 1-i]purin-7-yl]-1,2,3-octanetriol and 1-[3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[2, 1-i]purin-7-yl]-1,2-heptanediol, were isolated by reverse phase high-performance liquid chromatography and characterized on the basis of their UV, fluorescence, nuclear magnetic resonance, and mass spectrometry features. The reaction mechanism for the formation of the DDE-2'-deoxyadenosine adducts involves 2,4-decadienal epoxidation and subsequent addition to the N2 amino group of 2'-deoxyadenosine, followed by cyclization at the N-1 site. Adducts differ by the length of carbon side chain and the number of hydroxyl groups. The present data indicate that DDE can be epoxidized by peroxides, and the resulting products are able to form several adducts with 2'-deoxyadenosine and/or DNA. Endogenous DNA adduct formation can contribute to the already reported high cytotoxicity of DDE to mammalian cells.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26.077, CEP 05599-970 São Paulo, Brazil.
V M
VM
Carvalho
P
P
Di Mascio
I P
IP
de Arruda Campos
T
T
Douki
J
J
Cadet
M H
MH
Medeiros
D000447:Aldehydes / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry; D003839:Deoxyadenosines / Q000737:chemistry*; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular
C115182:1,N(6)-etheno-2'-deoxyadenosine; D000447:Aldehydes; D018736:DNA Adducts; D003839:Deoxyadenosines; C057349:2,4-decadienal; D004247:DNA; C058118:2'-deoxyadenosine