CLINICAL MODULATION OF OXIDATIVE DNA DAMAGE BY DIET

氧化性DNA损伤是正常代谢事件的结果。 这种类型的DNA损伤已被认为在内源性 致癌作用 因此，可以预计， 氧化性DNA损伤可用作癌症风险的标志。 乳腺 女性患癌症的风险与饮食中的脂肪和热量有关 摄入 在实验室动物中的乳腺肿瘤发生也已被证实。 显示受膳食脂肪和卡路里调节。 最近的研究 表明氧化性DNA损伤水平可以通过饮食调节。 的 饮食中脂肪和热量对乳腺癌风险的相对重要性 然而，人类仍然是未知的。 在这项研究中， 饮食中的脂肪和热量对DNA氧化损伤水平的影响 在饮食期间，将检查女性的外周有核血细胞。 变化 这些妇女将被随机分为四组， 12周：对照组、低脂组（15%的热量来自脂肪）、限制热量 (25%限制），以及低脂和卡路里限制的组合。 每两周一次的个性化饮食咨询将由 注册营养师 将对饮食进行计算机分析 每月一次，使用4天的食物记录。 作为氧化性 将定量DNA损伤、5-羟甲基尿嘧啶和8-羟基鸟嘌呤 通过气相色谱-质谱法测定有核血细胞DNA中的双周浓度 光谱法 2X2析因研究设计将允许 检测高血压组间有临床意义的差异 统计力量 脂肪和蛋白质的独立和协同作用 将评估卡路里对氧化DNA损伤水平的影响。 使用 氧化性DNA损伤作为一种中间标记， 评估饮食变化对降低癌症风险的影响。

Oxidative DNA damage occurs as a result of normal, metabolic events. This type of DNA damage has been suggested to play a role in endogenous carcinogenesis. It therefore may be expected that the levels of oxidative DNA damage can be used as a marker of cancer risk. Breast cancer risk in women has been associated with dietary fat and caloric intake. Mammary gland tumorigenesis in laboratory animals also has been shown to be modulated by dietary fat and calories. Recent studies have indicated the oxidative DNA damage levels can be modulated by diet. The relative importance of dietary fat and calories on breast cancer risk in humans, however, remains unknown. In this proposed study, the impact of dietary fat and calories on the levels of oxidative DNA damage levels in peripheral nucleated blood cells will be examined in women during dietary change. The women will be randomized to remain on one of four diets for 12 weeks: control, low-fat (15% of calories from fat), calorie-restricted (25% restriction), and a combination of low-fat and calorie-restricted. biweekly, individualized dietary counseling will be provided by registered dietitians. Computer analyses of the diet will be performed at monthly intervals using 4-day food records. As markers of oxidative DNA damage, 5 hydroxymethyluracil and 8-hydroxyguanine will be quantified biweekly in DNA from nucleated blood cells by gas chromatography-mass spectrometry. The 2X2 factorial study design will allow for the detection of clinically meaningful differences among groups with high statistical power. The independent and synergistic effects of fat and calories on oxidative DNA damage levels will be evaluated. Use of oxidative DNA damage as an intermediate marker will allow for the rapid assessment of the influence of dietary change on cancer risk reduction.