Interventions with antioxidants and nutrients in relation to oxidative DNA damage and repair

Interventions with antioxidants and nutrients in relation to oxidative DNA damage and repair
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DOI:
10.1016/j.mrfmmm.2004.02.018
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发表时间:
2004-07-13
影响因子:
2.3
通讯作者:
Loft, S
Loft, S
中科院分区:
医学4区
文献类型:
--
作者:
Moller, P;Loft, S

文献摘要

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细胞不断暴露于来自代谢和其他生化反应以及外部因素的氧化剂,这表明DNA修复系统和营养抗氧化剂是低水平DNA损伤和癌症风险的重要决定因素。单一的抗氧化剂,以及各种蔬菜,水果和类胡萝卜素和多酚丰富的产品,已经评估了生物标志物,主要包括DNA损伤的白色血细胞(WBC),尿排泄的氧化碱基和核苷和DNA修复能力。氧化性DNA损伤的基础水平和干预措施的影响是相当可变的,可能反映了人群、方案和测定类型的差异。一般而言,单剂量抗氧化剂干预已显示出对WBC DNA氧化的保护作用。持续摄入抗氧化剂的研究显示,对WBC中氧化性DNA损伤的影响结果不一,可能是由于设计、统计功效和周期效应的各种问题。仅对男性受试者进行的研究似乎显示出一致的抗氧化作用,即氧化嘧啶水平降低。对氧化应激受试者(例如HIV感染患者或糖尿病患者)的研究表明,在具有高初始水平氧化DNA损伤的人群中具有有益的结果。抗氧化剂对DNA修复酶的影响的最新研究表明,氧化嘌呤的清除增加,而相关DNA修复基因的mRNA水平似乎不受富含抗氧化剂的饮食影响。今后应注意干预研究的设计、性别效应、防御酶基因型和DNA修复能力的考虑。(C)2004 Elsevier B.V.保留所有权利。
Cells are constantly exposed to oxidants from metabolic and other biochemical reactions as well as external factors, suggesting that DNA repair systems and nutritional antioxidants are important determinants for low levels of DNA damage and cancer risk. The effects of single antioxidants, as well as various vegetables, fruits and carotenoid- and polyphenolic-rich products, have been assessed with biomarkers, mainly including DNA damage in white blood cells (WBC), urinary excretion of oxidized bases and nucleosides and DNA repair capacity. The basal levels of oxidative DNA damage, and effects of the interventions have been rather variable, possibly reflecting differences in the populations, regimens, and the type of assays. In general, single dose antioxidant interventions have shown protective effects with respect to WBC DNA oxidation. Studies with continuous ingestion of antioxidants show mixed results with respect to effects on oxidative DNA damage in WBC, possibly due to various problems with design, statistical power and period effects. Studies with only male subjects appear to show consistent antioxidant effects in terms of reduced levels of oxidized pyrimidines. Investigations of oxidatively stressed subjects, e.g. HIV-infected patients or diabetics, suggest beneficial outcomes in populations with high initial levels of oxidative DNA damage. Recent research on the effect of antioxidants on DNA repair enzymes Suggest effects in terms of increased removal of oxidized purines, whereas mRNA levels of the relevant DNA repair genes appears to be unaffected by an antioxidant-rich diet. In the future, care should be taken with respect to design of intervention studies and considerations of gender effect, genotypes of defence enzymes as well as DNA repair capacity. (C) 2004 Elsevier B.V. All rights reserved.