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，促进消除致癌物质和提高抗氧化能力。许多可食用植物，最值得注意的是3天大的西兰花芽，以异硫氰酸酯或其芥子油苷前体的形式含有有效的第2阶段酶诱导剂活性。在动物中，萝卜硫素，来自西兰花芽的主要硫代葡萄糖苷（萝卜硫苷），是一种非常有效的第二阶段酶活性诱导剂，并防止化学致癌作用。本研究的目的是在高风险人群中翻译和评价这些实验室结果。先前的试验提供了关于异硫氰酸酯的安全性、代谢和尿处置以及芥子油苷活化的重要信息。由于有可能种植具有一致的萝卜硫苷成分的西兰花芽，我们建议进行临床试验，以首次评估西兰花芽调节人类环境致癌物代谢的功效。本临床试验的目标人群是中华人民共和国启东市的居民，他们有发生肝细胞癌的高风险，部分原因是食用了被黄曲霉毒素污染的斯台普斯。西兰花芽的摄入能力，以减少尿排泄的黄曲霉毒素-DNA损伤产物将提供测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的有用性，调节表达的致癌物质解毒酶的手段，食品含有标准水平的植物化学物质作为一般的战略，在人类的化学预防。

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.