A formation mechanism for 8-hydroxy-2′-deoxyguanosine mediated by peroxidized 2′-deoxythymidine
A formation mechanism for 8-hydroxy-2′-deoxyguanosine mediated by peroxidized 2′-deoxythymidine
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DOI：
10.1016/j.freeradbiomed.2008.08.003
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发表时间：
2008-11-01
影响因子：
7.4
通讯作者：
Kanazawa, Kazuki
中科院分区：
文献类型：
--
作者：
Goto, Miho;Ueda, Keisuke;Kanazawa, Kazuki
DNA中8 - 羟基 - 2'- 脱氧鸟苷（8 - OHdG）的氧化形成与包括癌症在内的退行性疾病的诱发密切相关。然而，参与8 - OHdG形成的氧化剂种类尚未完全明确。基于过氧自由基是这种物质的有力候选者，我们使用2,2'- 偶氮二（2 - 脒基丙烷）（AAPH）作为过氧自由基发生器。小牛胸腺DNA暴露于AAPH会形成8 - OHdG，但单独的2'- 脱氧鸟苷（dG）暴露则不会。从各种核苷酸组合的暴露情况来看，只有在dG和胸苷（dT）存在的情况下才会形成8 - OHdG。dG与dT的所有氧化产物5 - （氢过氧甲基）- 2'- 脱氧尿苷混合会产生8 - OHdG，但生成量很少。相比之下，在AAPH存在下向过氧化的dT中加入dG会大量产生8 - OHdG。因此，8 - OHdG的形成是由过氧化的dT介导的。已知内源性过氧自由基是脂质过氧化物，而非人工的AAPH，它可能是体内由胸苷介导的8 - OHdG形成的氧化剂种类。（c）2008爱思唯尔公司。保留所有权利。
The oxidative formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA is closely associated with the induction of degenerative diseases, including cancer. However, the oxidant species participating in the formation of 8-OHdG has yet to be fully clarified. Oil the basis that peroxyl radicals are a strong candidate for this species, we employed 2,2'-azobis(2-amidinopropane) (AAPH) as a peroxyl radical generator. Exposure of calf thymus DNA to AAPH formed 8-OHdG, but the exposure of 2'-deoxyguanosine (dG) alone did not. From the exposure of various combinations of nucleotides, 8-OHdG was formed only in the presence of dG and thymidine (dT). A mix of dG with all oxidation product of dT, 5-(hydroperoxymethyl)-2'-deoxyuridine, produced 8-OHdG, but the amount formed was small. In contrast, 8-OHdG was produced abundantly by the addition of dG to peroxidized dT with AAPH. Thus, the formation of 8-OHdG was mediated by the peroxidized dT. Instead of artificial AAPH, endogenous peroxyl radicals are known to be lipid peroxides, which are probably the oxidant species for 8-OHdG formation mediated by thymidine ill vivo. (c) 2008 Elsevier Inc. All rights reserved.