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Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species.

机译:儿茶素通过产生活性氧来诱导对细胞和分离的DNA的氧化损伤。

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Green tea catechins have antimutagenic and anticarcinogenic activities. On the other hand, several epidemiological studies have indicated significant positive relationship between green tea consumption and cancer. Catechins enhance colon carcinogenesis in rats initiated with chemical carcinogen. To clarify the mechanism underlying the potential carcinogenicity, we investigated the DNA-damaging ability of catechins in human cultured cells. Catechin increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60 but not in HP100, a hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. The catechin-induced formation of 8-oxodG in HL-60 cells significantly decreased by bathocuproine. Furthermore, we investigated DNA damage and its site-specificity induced by catechins, using 32P-labeled DNA fragments. Catechin and epicatechin induced extensive DNA damage in the presence of Cu(II). Catechin caused piperidine-labilesites at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine inhibited the DNA damage, indicating the involvement of H2O2 and Cu(I). NADH enhanced catechins plus Cu(II)-induced 8-oxodG formation in calf thymus DNA, suggesting the redox cycle between catechins and their corresponding quinones, the oxidized forms of catechins. The DNA-damaging ability of epicatechin is stronger than that of catechin, possibly due to the greater turnover frequency of the redox cycle. The difference in their redox properties could be explained by their redox potentials estimated form an ab initio molecular orbital calculation. The present study demonstrated that catechins could induce metal-dependent H2O2 generation during the redox reactions and subsequently damage to cellular and isolated DNA. Therefore, it is reasonably considered that green tea catechins may have the dual function of anticarcinogenic and carcinogenic potentials.
机译:绿茶儿茶素具有抗诱变和抗癌活性。另一方面,一些流行病学研究表明,饮用绿茶与癌症之间存在显着的正相关。儿茶素能增强化学致癌物引发的大鼠结肠癌的发生。为了阐明潜在致癌性的机制,我们研究了人培养细胞中儿茶素的DNA破坏能力。儿茶素在人白血病细胞HL-60中增加了特征性氧化DNA损伤的8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG)的形成,但在过氧化氢(H2O2)HP100中却没有。 HL-60产生的耐药细胞系。儿茶素可显着减少儿茶素诱导的HL-60细胞中8-oxodG的形成。此外,我们使用32P标记的DNA片段调查了儿茶素引起的DNA损伤及其位点特异性。在Cu(II)存在下,儿茶素和表儿茶素会引起广泛的DNA损伤。在Cu(II)存在下,儿茶素在胸腺嘧啶和胞嘧啶残基上引起哌啶不稳定的位点。过氧化氢酶和浴铜嘌呤抑制DNA损伤,表明H2O2和Cu(I)参与。 NADH增强了小儿胸腺DNA中的儿茶素以及Cu(II)诱导的8-oxodG的形成,表明儿茶素与其相应的醌之间的氧化还原循环是儿茶素的氧化形式。表儿茶素的DNA破坏能力强于儿茶素,这可能是由于氧化还原循环的周转频率更高。它们的氧化还原特性的差异可以通过从头算分子轨道计算估算出的氧化还原电位来解释。本研究表明,儿茶素可以在氧化还原反应中诱导金属依赖性的H2O2生成,并随后破坏细胞和分离的DNA。因此,有理由认为绿茶儿茶素可能具有抗癌和致癌的双重功能。

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