Carvalho V M, Di Mascio P, de Arruda Campos I P, Douki T, Cadet J, Medeiros M H
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26.077, CEP 05599-970 São Paulo, Brazil.
Chem Res Toxicol. 1998 Sep;11(9):1042-7. doi: 10.1021/tx9800710.
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.
反，反-2,4-癸二烯醛（DDE）是脂质过氧化的一种重要分解产物。这种醛对哺乳动物细胞具有细胞毒性，并且已知与DNA损伤有关。因此，本研究尝试评估DDE与2'-脱氧腺苷（dAdo）的反应活性。结果表明，DDE能够与2'-脱氧腺苷结合，产生高荧光产物。除了1,N6-乙烯基-2'-脱氧腺苷（εdAdo）外，通过反相高效液相色谱法分离出另外两种相关加合物，即1-[3-(2-脱氧-β-D-赤藓糖基)-3H-咪唑并[2,1-i]嘌呤-7-基]-1,2,3-辛三醇和1-[3-(2-脱氧-β-D-赤藓糖基)-3H-咪唑并[2,1-i]嘌呤-7-基]-1,2-庚二醇，并根据它们的紫外、荧光、核磁共振和质谱特征对其进行了表征。DDE-2'-脱氧腺苷加合物形成的反应机制包括2,4-癸二烯醛环氧化，随后加成到2'-脱氧腺苷的N2氨基上，接着在N-1位点环化。加合物的区别在于碳侧链的长度和羟基的数量。目前的数据表明，DDE可被过氧化物环氧化，生成的产物能够与2'-脱氧腺苷和/或DNA形成多种加合物。内源性DNA加合物的形成可能导致已报道的DDE对哺乳动物细胞的高细胞毒性。
