Chemopreventive Efficacy of Broccoli Sprouts 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，证明水果和蔬菜的消费量与患癌症的风险之间存在负相关关系。保护的一个主要机制是诱导第二阶段解毒酶，促进致癌物的消除和提高抗氧化能力。许多可食用植物，尤其是3天大的西兰花芽，以异硫氰酸酯或其硫代葡萄糖苷前体的形式含有有效的第二相酶诱导活性。在动物中，萝卜硫素是从西兰花芽中主要的硫代葡萄糖苷(硫代萝卜素)中提取的，是一种非常有效的2相酶活性诱导剂，可以防止化学致癌。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。以前的试验已经提供了关于异硫氰酸酯的安全性、代谢和尿液处置以及硫代葡萄糖苷的激活的重要信息。由于可以种植具有稳定的葡萄糖萝卜素成分的西兰花芽，我们建议进行一项临床试验，以提供对西兰花芽调节人类环境致癌物质新陈代谢的首次疗效评估。这项临床试验的目标人群是中华人民共和国中国启东的居民，他们患肝细胞癌的风险很高，部分原因是他们食用了受黄曲霉毒素污染的主食。摄取西兰花芽的能力以减少尿液中黄曲霉毒素-DNA损伤产物的排泄，将为衡量干预效果提供主要手段。这项临床试验将对通过含有标准化水平的植物化学物质的食物来调节致癌解毒酶的表达作为人类化学预防的一般策略的有用性进行严格的评估。

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.