EFFECT TEA CONSUMP ON PHIP BIOAVIAL AT ULTR-LOW DOSE IN HUMAN VOL

超低剂量的茶摄入量对人体体积中 PHIP 生物病毒的影响

• 批准号: 7602424
• 负责人: Roderick H Dashwood
• 金额: $ 2.1万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602424
• 关键词: 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine; Alcoholic Beverages; Area Under Curve; Beverages; Blood; Caffeine; Chickens; Code; Computer Retrieval of Information on Scientific Projects Database; DNA Adduction; DNA Adducts; Dose; Eating; Excision; Exposure to; Funding; Gelatin; Glucuronides; Grant; High Pressure Liquid Chromatography; Hour; Human; Individual; Institution; Label; Laboratories; Meat; Multivariate Analysis; Numbers; Ontario; Persons; Proteins; Protocols documentation; Radiation; Radioactive; Rate; Research; Research Personnel; Resources; Sampling; Serum; Shipping; Ships; Source; Tea; United States National Institutes of Health; Urine; Water; Week; adduct; base; capsule; chlorophyllin; cooking; day; design; dietary restriction; drinking; glucuronide; interest; protective effect; research study; treatment planning; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study seeks to show a protective effect of tea in people consuming a dietary-relevant dose of PhIP, a carcinogenic compound from cooked meat. The design calls for 2-5 volunteers and is based on standardized protocols by our collaborators in Lawrence Livermore National Laboratory (LLNL). Five treatments are planned: PhIP, PhIP plus tea, PhIP plus decaffeinated tea, PhIP plus caffeine, and PhIP plus chlorophyllin (CHL), with washout periods between each cycle. 14C-labeled PhIP (Toronto Res, Ontario) will be administered orally in gelatin capsules at a dose of 70 mg per person (sp.act. 56 mCi/mmol); the dose of PhIP is equivalent to eating ~175g of well-done chicken, and the radioactive dose is equivalent to less than one day of exposure to background sources of radiation. Volunteers will follow a restricted diet for one week prior to each cycle and will fast overnight, as well as during the hours of 8-10 AM on the day of the experiment. For three days prior to each study cycle, volunteers will consume 5-6 cups per day of a hot beverage (water, or tea provided by the study) and refrain from drinking other tea or any caffeine-containing beverages and from alcoholic beverages. Normal eating and drinking will resume at noon. During 8-10 AM, each person will consume 3 cups of water or tea (750 ml total) before taking PhIP; in subsequent rounds, the equivalent amount of decaffeinated tea will be drunk, or caffeine with water. Finally, CHL will be given in water (150 mg Rystan). Blood (2-10 ml) will be drawn at -.25, 0.75, 1, 2, 8, 24, & 48 hours, and pooled urine samples will be collected at -.25, 1, 2, 3, 4, 5, 6, 7, 8, and 24 hours. Cycles will occur every second week, or when 14C levels return to baseline. Coded serum and urine samples will be shipped to LLNL. Total PhIP levels and the profile of PhIP metabolites will be ascertained by HPLC, and protein and DNA adduct levels will be determined by AMS. The small number of individuals does not allow for a multivariate analysis; however, exploratory analyses will be conducted to generate hypotheses. Of interest will be modulator effects on specific metabolites (e.g. PhIP-glucuronides), the rate of protein and DNA adduct formation and removal, and total adducts formed (area under the curve).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究旨在证明茶对食用饮食相关剂量的PhIP（一种来自熟肉的致癌化合物）的人的保护作用。 该设计需要2-5名志愿者，并基于劳伦斯利弗莫尔国家实验室（LLNL）合作者的标准化方案。 计划进行五种治疗：PhIP、PhIP加茶、PhIP加脱咖啡因茶、PhIP加咖啡因和PhIP加叶绿酸（CHL）， 洗脱 每个周期之间的时间。 14 C标记的PhIP（多伦多Res，安大略）将以明胶胶囊口服给药，剂量为70 mg/人（sp.act. 56 mCi/mmol）; PhIP的剂量相当于吃下约175克熟透的鸡肉，放射性剂量相当于暴露于本底辐射源不到一天。志愿者将在每个周期之前遵循限制饮食一周，并将禁食过夜，以及在实验当天上午8-10点期间。在每个研究周期之前的三天，志愿者将每天饮用5-6杯热饮（水或研究提供的茶），并避免饮用其他茶或任何含咖啡因的饮料以及酒精饮料。中午恢复正常饮食。 在上午8-10点，每个人在服用PhIP之前将饮用3杯水或茶（共750毫升）;在随后的几轮中，将饮用等量的无咖啡因茶，或咖啡因水。 最后，将给予CHL水溶液（150 mg Rystan）。 在-0.25、0.75、1、2、8、24和48小时抽取血液（2-10 ml），并在-0.25、1、2、3、4、5、6、7、8和24小时收集合并的尿样。 周期将每两周发生一次，或者当14 C水平恢复到基线时发生。将编码的血清和尿液样本运送至LLNL。 将通过HPLC确定总PhIP水平和PhIP代谢产物谱，并通过AMS测定蛋白质和DNA加合物水平。 由于个体数量较少，无法进行多变量分析;但是，将进行探索性分析以生成假设。 感兴趣的是对特定代谢物（例如PhIP-葡萄糖醛酸苷）的调节作用、蛋白质和DNA加合物形成和去除的速率以及形成的总加合物（曲线下面积）。