CLINICAL MODULATION OF OXIDATIVE DNA DAMAGE BY DIET

饮食对 DNA 氧化损伤的临床调节

• 批准号: 2101581
• 负责人: Zora Djuric
• 金额: $ 16.67万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-21 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2101581
• 关键词: DNA damage; age difference; alcoholic beverage consumption; biomarker; blood chemistry; body composition; breast neoplasms; caloric dietary content; cancer prevention; cancer risk; clinical trials; contraceptives; dietary constituent; dietary lipid; female; gas chromatography mass spectrometry; human subject; nutrition related neoplasm /cancer; nutrition related tag; oxidative stress; questionnaires; racial /ethnic difference; statistics /biometry; tobacco abuse

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.

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损伤中发挥作用。 致癌作用。 因此，可以预期， DNA 氧化损伤可作为癌症风险的标志。 胸部 女性癌症风险与膳食脂肪和热量有关 摄入量。 实验动物乳腺肿瘤的发生也已被证实 显示受膳食脂肪和卡路里的调节。 最近的研究有 表明 DNA 氧化损伤水平可以通过饮食调节。 这 膳食脂肪和热量对乳腺癌风险的相对重要性 然而，人类仍然未知。 在这项拟议的研究中， 膳食脂肪和热量对氧化 DNA 损伤水平的影响 将在饮食期间检查女性的外周有核血细胞 改变。 这些女性将被随机选择保持四种饮食中的一种 12周：控制、低脂（15%的热量来自脂肪）、热量限制 （25% 限制），以及低脂和热量限制的组合。 每两周一次，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。 作为氧化标志物 DNA损伤、5羟甲基尿嘧啶和8-羟鸟嘌呤将被定量 每两周一次通过气相色谱-质谱法检测有核血细胞的 DNA 光谱测定法。 2X2 因子研究设计将允许 检测高组之间有临床意义的差异 统计功效。 脂肪和脂肪的独立作用和协同作用 将评估卡路里对氧化 DNA 损伤水平的影响。 使用 氧化 DNA 损伤作为中间标记将允许快速 评估饮食变化对降低癌症风险的影响。