Chemopreventive Efficacy of Broccoli Sprouts in Humans

西兰花芽对人类的化学预防功效

• 批准号: 6562925
• 负责人: THOMAS W KENSLER
• 金额: $ 21.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-13 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6562925
• 关键词: China; Cruciferae; DNA damage; aflatoxins; antioxidants; biomarker; cancer prevention; cancer risk; chemical carcinogen; chemoprevention; clinical research; clinical trials; data collection methodology /evaluation; diet therapy; electrospray ionization mass spectrometry; enzyme induction /repression; hepatocellular carcinoma; high performance liquid chromatography; human therapy evaluation; isothiocyanates; liquid chromatography mass spectrometry; nutrition related tag; statistics /biometry; toxin metabolism; urinalysis

DESCRIPTION (provided by applicant): Epidemiological studies provide convincing evidence for an inverse relation between quantities of fruit and vegetables consumed and the risk of developing cancer. A major mechanism for protection involves induction of phase 2 detoxication enzymes that promote elimination of carcinogens and boost antioxidant capacity. Many edible plants, most notably 3-day-old broccoli sprouts, contain potent phase 2 enzyme inducer activity in the form of isothiocyanates or their glucosinolate precursors. In animals, sulforaphane, derived from the principal glucosinolate (glucoraphanin) of broccoli sprouts, is a very potent inducer of phase 2 enzyme activity and protects against chemical carcinogenesis. The objective of this study is to translate and evaluate these laboratory findings in a high-risk human population. Previous trials have afforded important information on the safety, metabolism and urinary disposition of isothiocyanates, and on the activation of glucosinolates. Since it is possible to grow broccoli sprouts with a consistent composition of glucoraphanin, we propose to conduct a clinical trial to provide the first assessment of the efficacy of broccoli sprouts to modulate the metabolism of an environmental carcinogen in humans. The target population for this clinical trial is residents of Qidong, People's Republic of China, who are at high risk for development of hepatocellular carcinoma, in part from consumption of dietary staples contaminated with aflatoxins. The capacity of ingestion of broccoli sprouts to reduce the urinary excretion of aflatoxin-DNA damage products will provide the primary means for measuring efficacy of the intervention. This clinical trial will provide a rigorous assessment of the usefulness of modulating expression of carcinogen detoxication enzymes by means of a food containing a standardized level of a phytochemical as a general strategy for chemoprevention in humans.

描述（由申请人提供）：流行病学研究提供了令人信服的证据，证明了消耗的水果和蔬菜与患癌症的风险之间存在反向关系。保护的主要机制涉及诱导2期解毒酶，以促进消除致癌物并增强抗氧化能力。许多可食用的植物，最著名的是3天大的西兰花新芽，都以异硫氰酸酯或其葡萄糖苷酸前体的形式包含有效的2期酶诱导剂活性。在动物中，西兰花芽孢杆菌的主要葡萄糖苷（葡萄糖磷酸）衍生的硫烷是一种非常有效的2期酶活性的诱导剂，可预防化学癌变。这项研究的目的是在高危人群中翻译和评估这些实验室发现。先前的试验提供了有关异硫氰酸酯的安全性，代谢和尿性处置以及葡萄糖醇酸酯激活的重要信息。由于有可能种植具有葡萄糖磷酸蛋白成分的西兰花芽孢杆菌，因此我们建议进行临床试验，以首先评估西兰花芽孢杆菌调节环境致癌物在人类中的代谢的疗效。这项临床试验的目标人群是中华人民共和国Qidong的居民，他们的肝细胞癌发育高，部分原因是消费饮食中的饮食丁香剂受到黄曲霉毒素的污染。摄取西兰花芽孢杆菌减少黄曲霉毒素-DNA损伤产物尿排泄的能力将为测量干预效率的效率提供主要手段。这项临床试验将通过含有标准化水平的植物化学水平作为人类化学预防的一般策略的食物来对调节致癌解毒酶的表达的有用性进行严格评估。