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).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究旨在在食用饮食中与饮食中剂量相关的人（一种煮熟的肉类的致癌化合物）中显示出茶的保护作用。 该设计要求2-5名志愿者，并基于我们劳伦斯·利弗莫尔国家实验室（LLNL）合作者的标准化协议。 计划了五种治疗方法：PHIP，PHIP加茶，PHIP加咖啡因的茶，Phip Plus咖啡因和PHIP加氯脂蛋白（CHL），每个周期之间的冲洗周期。 14C标记的PHIP（多伦多Res，安大略省）将以每人70毫克的剂量口服明胶胶囊（SP.ACT。56MCI/mmol）； pHIP的剂量等于食用〜175克做好的鸡肉，放射性剂量等效于不到一天暴露于背景辐射源的一天。志愿者将在每个周期前一周遵循限制饮食，并将在实验当天的8-10 AM的时间过夜，并将在晚上的饮食中进行限制。在每个研究周期前的三天内，志愿者每天将每天喝5-6杯热饮料（研究提供的水或茶），并不要喝其他茶或任何含咖啡因的饮料和酒精饮料。正常的饮食将在中午恢复。 在上午8-10时，每个人在服用PHIP之前将消耗3杯水或茶（总计750毫升）；在随后的一轮中，等效的脱咖啡因将醉酒，或用水咖啡因。 最后，CHL将在水（150 mg rystan）中给出。 血液（2-10 mL）将以-.25、0.75、1、2、8、24和48小时的含量​​抽取，并以-.25、2、2、3、4、5、6、7、8和24小时收集合并的尿液样品。 周期每隔第二周或14C水平返回基线时发生。编码的血清和尿液样品将运送到LLNL。 HPLC将确定pHIP水平和pHIP代谢产物的特征，蛋白质和DNA加合物水平将由AMS确定。 少数个体不允许进行多元分析；但是，将进行探索性分析以产生假设。 感兴趣的是调节剂对特定代谢产物（例如pHIP-葡萄糖醛酸苷），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（曲线下的面积）。