CLINICAL MODULATION OF OXIDATIVE DNA DAMAGE BY DIET

饮食对 DNA 氧化损伤的临床调节

• 批准号: 2101582
• 负责人: Zora Djuric
• 金额: $ 18.07万
• 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/2101582
• 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.

正常的代谢事件导致氧化DNA损伤发生。 已经建议这种DNA损伤在内源性中发挥作用 致癌作用。 因此，可能会期望 氧化性DNA损伤可以用作癌症风险的标志。 胸部 女性的癌症风险与饮食脂肪和热量有关 进气。 实验动物中的乳腺肿瘤发生也已经 被证明是由饮食脂肪和卡路里调节的。 最近的研究 指出氧化DNA损伤水平可以通过饮食调节。 这 饮食脂肪和卡路里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， 饮食脂肪和卡路里在氧化DNA损伤水平的水平上 饮食中，将在女性中检查外周核细胞的外周核细胞 改变。 这些妇女将被随机保留在四种饮食中之一 12周：对照，低脂（脂肪卡路里的15％），限制卡路里 （25％限制），以及低脂和限制卡路里的组合。 双周，个性化的饮食咨询将由 注册营养师。 将对饮食进行计算机分析 每月使用4天的食物记录。 作为氧化的标记 将定量DNA损伤，5个羟甲基鲁氨基酸和8-羟基鸟嘌呤 通过气相色谱质量从成核血细胞中双周在DNA中 光谱法。 2x2阶乘研究设计将允许 检测高较高的群体中临床意义的差异 统计能力。 脂肪和 将评估氧化DNA损伤水平的卡路里。 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。