CLINICAL MODULATION OF OXIDATIVE DNA DAMAGE BY DIET

DNA氧化损伤是正常代谢事件的结果。 这种类型的DNA损伤被认为在内源性 致癌。因此可以预期的是， DNA氧化损伤可以作为癌症风险的标志。乳房 女性患癌症的风险与饮食中的脂肪和热量有关 入口处。实验动物的乳腺肿瘤发生也一直是 显示出受饮食脂肪和卡路里的调节。最近的研究表明 提示饮食可以调节DNA氧化损伤水平。这个 饮食中脂肪和卡路里对乳腺癌风险的相对重要性 然而，人类仍然是未知的。在这项拟议的研究中， 膳食脂肪和卡路里对小鼠DNA氧化损伤水平的影响 妇女在饮食期间将检查外周血有核细胞 变化。这些女性将被随机分配到以下四种饮食中的一种 12周：对照组，低脂(15%卡路里来自脂肪)，卡路里限制 (25%限制)，以及低脂肪和卡路里限制的组合。 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。作为氧化的标志物 DNA损伤、5-羟甲基尿嘧啶和8-羟基鸟嘌呤将被量化 用气相色谱-质谱法从有核血细胞中提取DNA 光谱分析。2X2析因研究设计将允许 高血压病患者组间临床意义差异的检测 统计学上的力量。脂肪和脂肪的独立和协同作用 将对氧化DNA损伤水平的卡路里进行评估。使用 氧化DNA损伤作为中间标记物将允许快速 评估饮食改变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.