USE OF ANTIOXIDANT SUPPLEMENTS AND OXIDATIVE DNA DAMAGE

描述（由申请人提供）：本申请的目的是研究使用含抗氧化剂的膳食补充剂与DMA损伤和修复的相关性。这是一个重要的研究领域，因为1亿美国人使用膳食补充剂，尽管缺乏明确的证据证明其有益或有害，但B-胡萝卜素对吸烟者的已知不良影响除外。我们对膳食补充剂对DNA损伤和修复（已知与癌症风险相关）的影响特别感兴趣，因为这种损伤可以通过营养因素，特别是抗氧化剂来减轻。由于补充剂的营养剂量通常是均衡饮食中可用剂量的10至100倍，因此与非使用者相比，高剂量补充剂使用者的抗氧化剂剂量与DNA损伤和修复能力之间的关系的性质和程度可能不同。这些问题以前没有在流行病学调查中进行过研究。我们假设使用含抗氧化剂的膳食补充剂（维生素C，维生素E，B-胡萝卜素和硒）与低水平的DNA损伤和高DNA修复能力有关。我们还假设使用促氧化剂补充剂（铁）与高水平的DNA损伤和低DNA修复能力有关。为了验证这些假设，我们将使用单细胞凝胶电泳（彗星试验）来测量220名年龄在50-74岁之间的健康成年人外周血标本中的DNA损伤和修复能力，这些成年人是膳食补充剂和癌症风险队列研究（R 01 CA 74846）的参与者。收集并分析以下数据，并将提供抗氧化剂暴露信息：根据家访清单测量的膳食补充剂使用;根据食物频率问卷测量的日常饮食;以及基于生物标志物的血清维生素E（a和y生育酚）、维生素C和类胡萝卜素以及趾甲硒的测量。作为本研究的一部分，将使用彗星试验在存档的外周血标本中测量DNA损伤和修复的结局。彗星试验是一种快速、经济和可靠的试验，可测量单个细胞中的DNA损伤和修复。该测定非常适合用于流行病学调查。我们的研究设计将有助于研究多种类型的补充剂，给定补充剂的剂量反应效应，几种补充剂的组合以及补充剂中的抗氧化剂与食物中的抗氧化剂在DNA损伤和修复方面的相互作用。

DESCRIPTION (provided by applicant): The objective of this application is to investigate the association of use of antioxidant-containing dietary supplements with DMA damage and repair. This is an important area of research because 100 million Americans use dietary supplements despite the lack of definitive evidence for benefit or harm, with the exception of known adverse effects of B-carotene in smokers. We are particularly interested in the influence of dietary supplements on DNA damage and repair (known to be associated with cancer risk) since such damage can be mitigated by nutritional factors, especially antioxidants. Because the nutrient dose from supplements is often 10 to 100 times the dose available from a balanced diet, the nature and magnitude of the associations of antioxidant dose with DNA damage and repair capacity may be different for high-dose supplement users, compared to non-users. These questions have not been previously examined in epidemiologic investigations. We hypothesize that use of antioxidant-containing dietary supplements (vitamin C, vitamin E, B-carotene and selenium) is associated with low levels of DNA damage and high DNA repair capacity. We also hypothesize that use of prooxidant supplements (iron) is associated with high levels of DNA damage and low DNA repair capacity. To test these hypotheses, we will use single cell gel electrophoresis (the comet assay) to measure DNA damage and repair capacity in peripheral blood specimens of 220 healthy adults aged 50-74 years who are participants in A Cohort Study of Dietary Supplements and Cancer Risk (R01 CA74846). The following data are collected and analyzed and will provide antioxidant exposure information: dietary supplement use measured from a home visit inventory; usual diet from a food frequency questionnaire; and biomarker based measures of serum vitamin E (a and y tocopherol), vitamin C and carotenoids and toenail selenium. The outcome, DNA damage and repair, will be measured as part of this study in archived peripheral blood specimens using the comet assay. The comet assay is a rapid, economical and reliable assay that measures DNA damage and repair in individual cells. This assay is very well suited for use in epidemiologic investigations. Our study design will facilitate the ability to investigate multiple types of supplements, dose-response effects for a given supplement, combinations of several supplements and interactions of antioxidants from supplements with antioxidants from food in relation to DNA damage and repair.