This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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).
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