Vm. Carvalho et al., FORMATION OF 1,N-6-ETHENO-2'-DEOXYADENOSINE ADDUCTS BY TRANS,TRANS-2,4-DECADIENAL, Chemical research in toxicology, 11(9), 1998, pp. 1042-1047
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.