Green tea catechins partially protect DNA from (.)OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals

Green tea catechins partially protect DNA from (.)OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals
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DOI:
10.1093/carcin/22.8.1189
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发表时间:
2001-08-01
期刊:
影响因子:
4.7
通讯作者:
Packer, JE
Packer, JE
中科院分区:
医学2区
文献类型:
--
作者:
Anderson, RF;Fisher, LJ;Packer, JE

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儿茶素、(-)-表儿茶素(EC)、(-)-表没食子儿茶素(EGC)、(-)-表儿茶素没食子酸酯(ECG)和(-)-表没食子儿茶素没食子酸酯(EGCG)被认为是绿色茶的活性成分,解释了所报道的某些癌症的化学预防。测量的低浓度(约。微摩尔)的儿茶素在人体中可以降低致癌的发生率尚不清楚。使用体外质粒DNA系统和放射性产生活性氧(ROS)在恒定的清除条件下,我们已经表明,所有四种儿茶素,当存在于低浓度,改善持续的DNA自由基损伤。通过随后与DNA糖基化酶甲酰氨基嘧啶(FPG)、内切核酸酶III(EndoIII)和5 ' AP内切核酸酶外切核酸酶III(ExoIII)孵育,观察到DNA单链断裂和DNA碱基残留损伤的减少。EGCG被认为是最活跃的儿茶素,在微摩尔浓度下观察到效果。结合快速反应化学研究支持的电子转移(或H-原子转移)从儿茶素的ROS诱导的自由基网站上的DNA的机制。这些结果支持儿茶素在与DNA自由基的直接相互作用中的抗氧化作用。
The catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) are believed to be active constituents of green tea accounting for the reported chemoprevention of certain cancers. The molecular mechanisms by which the measured low concentrations (ca. micromolar) of catechins in humans can reduce the incidence of carcinogenesis is not clear. Using an in vitro plasmid DNA system and radiolytically generating reactive oxygen species (ROS) under constant scavenging conditions, we have shown that all four catechins, when present at low concentrations, ameliorate free radical damage sustained by DNA. A reduction in both prompt DNA single-strand breaks and residual damage to the DNA bases, detected by subsequent incubation with the DNA glycosylases formamidopyrimidine (FPG), endonuclease III (EndoIII) and 5 ' AP endonuclease exonuclease III (ExoIII), was observed. EGCG was found to be the most active of the catechins, with effects seen at micromolar concentrations. Combined fast-reaction chemistry studies support a mechanism of electron transfer (or H-atom transfer) from catechins to ROS-induced radical sites on the DNA. These results support an antioxidant role for catechins in their direct interaction with DNA radicals.