Redox-linked effects of green tea on DNA damage and repair, and influence of microsatellite polymorphism in HMOX-1: results of a human intervention trial
Redox-linked effects of green tea on DNA damage and repair, and influence of microsatellite polymorphism in HMOX-1: results of a human intervention trial
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DOI：
10.1093/mutage/geu022
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发表时间：
2015-01-01
期刊：
影响因子：
2.7
通讯作者：
Benzie, Iris F. F.
中科院分区：
文献类型：
--
作者：
Choi, Siu-Wai;Yeung, Vincent T. F.;Benzie, Iris F. F.
据报道，绿色茶具有许多健康益处，包括基因保护和抗氧化作用，但绿色茶在体外具有促氧化活性。人们已经假设茶诱导的促氧化剂转变会引发细胞保护性适应，但缺乏人体数据。我们在一项随机、安慰剂对照、交叉补充试验中研究了对氧化诱导的DNA损伤和氧化还原相关细胞保护因子的影响，包括淋巴细胞中的8-氧代鸟嘌呤糖基化酶（hOGG 1）和血红素加氧酶1（HMOX-1）。hOGG 1催化碱基切除修复的第一步;增加的HMOX-1是对促氧化剂变化的细胞保护反应的标志。还探讨了HMOX-1启动子区微卫星多态性的影响。据报道，该区域中较高数量的GT重复[GT（n）]减少了对促氧化剂变化的响应。43名2型糖尿病受试者{20名短[S/S; GT（n）< 25]和23名长[L/L; GT（n）a份/千日元25]}服用绿色茶[2 × 150 ml 1%w/v茶/天（或水作为对照）] 12周。在每次治疗前后采集空腹静脉血。甲酰胺嘧啶DNA糖基化酶辅助彗星试验用于测量淋巴细胞中的DNA损伤。为了测量hOGG 1活性，我们使用与来自测试对象的淋巴细胞提取物一起孵育的光损伤的HeLa细胞，结合彗星试验。还研究了淋巴细胞HMOX-1和hOGG 1蛋白浓度以及氧化还原敏感基因（包括HMOX-1和hOGG 1）的表达（mRNA）。结果表明，饮茶后DNA损伤程度降低（约15%），hOGG 1活性升高（约50%），HMOX-1蛋白含量升高（约40%），差异有显著性（P < 0.01）。未观察到mRNA表达的变化。S/S组的基线HMOX-1蛋白和hOGG 1活性较高（P < 0.05），但两个GT（n）组的茶相关反应相似。绿色茶与降低DNA损伤、增加hOGG 1活性和提高HMOX-1蛋白水平明显相关。需要进一步的研究来确认因果关系，并确定这些影响是否是由蛋白质的翻译后变化或基因表达增加介导的。
Green tea has many reported health benefits, including genoprotective and antioxidant effects, but green tea has pro-oxidant activity in vitro. A tea-induced pro-oxidant shift that triggers cytoprotective adaptations has been postulated, but human data are lacking. We investigated effects on oxidation-induced DNA damage and redox-linked cytoprotective factors, including 8-oxoguanine glycosylase (hOGG1) and heme oxygenase 1 (HMOX-1) in lymphocytes in a randomised, placebo-controlled, cross-over supplementation trial. hOGG1 catalyses the first step in base excision repair; increased HMOX-1 is a sign of cytoprotective response to pro-oxidant change. The influence of microsatellite polymorphisms in the HMOX-1 promoter region was also explored. Higher numbers of GT repeats [GT(n)] in this region reportedly diminish response to pro-oxidant change. Green tea [2x150ml of 1% w/v tea/day (or water as control)] was taken for 12 weeks by 43 Type 2 diabetes subjects {20 with short [S/S; GT(n) < 25] and 23 with long [L/L; GT(n) a parts per thousand yen 25]}. Fasting venous blood was collected before and after each treatment. The formamidopyrimidine DNA glycosylase-assisted comet assay was used to measure DNA damage in lymphocytes. For measuring hOGG1 activity, we used photo-damaged HeLa cells incubated with lymphocyte extracts from test subjects, in combination with the comet assay. Lymphocyte HMOX-1 and hOGG1 protein concentrations and expression (mRNA) of redox-sensitive genes, including HMOX-1 and hOGG1, were also investigated. Results showed significantly (P < 0.01) lower (similar to 15%) DNA damage, higher (similar to 50%) hOGG1 activity and higher (similar to 40%) HMOX-1 protein concentration after tea. No changes in mRNA expression were seen. Baseline HMOX-1 protein and hOGG1 activity were higher (P < 0.05) in the S/S group, but tea-associated responses were similar in both GT(n) groups. Green tea is clearly associated with lowered DNA damage, increased hOGG1 activity and higher HMOX-1 protein levels. Further study is needed to confirm a cause and effect relationship and to establish if these effects are mediated by post-translational changes in proteins or by increased gene expression.