Formation of 1,N6-etheno-2′-deoxyadenosine adducts by trans,trans-2,4-decadienal

被引:23
作者
Carvalho, VM
Di Mascio, P
Campos, IPD
Douki, T
Cadet, J
Medeiros, MHG [1 ]
机构
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, CP 26-077, BR-05599970 Sao Paulo, Brazil
[2] Univ Paulista, Inst ciencias Exatas & Tecnol, BR-06500000 Sao Paulo, Brazil
[3] CEA, LAN, Dept Rech Fondamentale Mat Condensee, SCIB, F-38054 Grenoble 9, France
关键词
D O I
10.1021/tx9800710
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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,N-6-etheno-2'-deoxyadenosine (epsilon dAdo), 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 N-2 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.
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页码:1042 / 1047
页数:6
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