Anderson R F, Fisher L J, Hara Y, Harris T, Mak W B, Melton L D, Packer J E
Department of Chemistry and Auckland Cancer Society Research Centre, University of Auckland, Private Bag 92019, Auckland 1, New Zealand.
Carcinogenesis. 2001 Aug;22(8):1189-93. doi: 10.1093/carcin/22.8.1189.
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.
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）被认为是绿茶的活性成分，这解释了绿茶对某些癌症具有化学预防作用的报道。人体内测得的低浓度（约微摩尔级）儿茶素能够降低癌症发生率的分子机制尚不清楚。我们使用体外质粒DNA系统，并在持续清除条件下通过辐射产生活性氧（ROS），结果表明，所有这四种儿茶素在低浓度时，均可减轻DNA遭受的自由基损伤。通过随后与DNA糖基化酶甲酰胺嘧啶（FPG）、核酸内切酶III（EndoIII）和5' AP核酸内切酶核酸外切酶III（ExoIII）一起孵育检测到，即时DNA单链断裂以及对DNA碱基的残留损伤均有所减少。结果发现，EGCG是最具活性的儿茶素，在微摩尔浓度时即可观察到其效果。结合快速反应化学研究表明，存在一种从儿茶素到DNA上ROS诱导的自由基位点的电子转移（或氢原子转移）机制。这些结果支持了儿茶素在与DNA自由基直接相互作用中所起的抗氧化作用。
