Chemopreventive Efficacy of Broccoli Sprouts in Humans

西兰花芽对人类的化学预防功效

• 批准号: 6758610
• 负责人: THOMAS W KENSLER
• 金额: $ 24.53万
• 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 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6758610
• 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，证明水果和蔬菜的摄入量与患癌症的风险之间存在反比关系。一个主要的保护机制涉及诱导第二阶段解毒酶，促进消除致癌物和提高抗氧化能力。许多可食用植物，尤其是3天的西兰花芽，含有有效的2期酶诱导剂活性，其形式是异硫氰酸酯或其硫代葡萄糖苷前体。在动物中，萝卜硫素是从西兰花芽中的主要硫代葡萄糖苷（glucoraphanin）中提取的，是一种非常有效的2期酶活性诱导剂，可以防止化学致癌。本研究的目的是在高危人群中翻译和评估这些实验室发现。先前的试验已经提供了关于异硫氰酸酯的安全性、代谢和尿态以及硫代葡萄糖苷活化的重要信息。由于有可能种植含有一致硫代萝卜苷成分的西兰花芽，我们建议进行一项临床试验，首次评估西兰花芽调节人类环境致癌物代谢的功效。这项临床试验的目标人群是中华人民共和国启东市的居民，他们患肝细胞癌的风险很高，部分原因是食用了受黄曲霉毒素污染的主食。摄入西兰花芽减少黄曲霉毒素- dna损伤产物尿排泄的能力将提供衡量干预效果的主要手段。这项临床试验将提供一个严格的评估，通过一种含有标准水平植物化学物质的食物来调节致癌物质解毒酶的表达，作为人类化学预防的一般策略。