2007 Annual Report 1a.Objectives (from AD-416) Develop algorithm relating increase in stable plasma Se level to that at baseline and level of supplemental Se. 1b.Approach (from AD-416) Conduct a randomized, double-blind, intervention study will be conducted with healthy men (120) and women (120) randomized to 0, 50, 100, or 200 ug Se/day (as L-selenomethionine) administered in daily oral doses. Fasting blood samples and urine samples will be drawn two wks prior to and periodically throughout the 1-yr study. The following measurements will be made: Se, homocysteine, vitamin B12 and folate in plasma; Se and 8a-deoxyquanosine in urine; DNA damage and allelic variants of Se-dependent enzymes in lymphocytes. Results will be used to compute the relationship of final-plateau plasma (9-12 mos.) Se concentration as a function of baseline (0 mos.) Se level, Se dose, metabolic body size and urinary Se, as well as outcomes related to carcinogenesis. 3.Progress Report This report serves to document research conducted under an interagency reimbursable agreement between ARS and National Cancer Institute of the National Institutes of Health. Additional details of research can be found in the report for the parent project 5450-51000-036-00D. This collaboration planned and implemented the first clinical intervention trial using nutritional doses of selenium, the "LoDoSe trial", which was initiated in FY2006 and will continue through FY2008. This trial will provide the fundamental information to allow the projection of daily dietary selenium needs from plasma selenium levels found to be thresholds for such health effects as minimalization of cancer risks in healthy Americans, which prospect has direct implications to the US food industry which can produce foods capable of providing 50-100 mcg selenium per day through geographic sourcing, or selenium-fortification. This year, 253 adult men and women volunteers participated in the intervention, with all completing the 1-yr intervention phase of the trial by the end of FY 2007. Studies of the baseline characteristics of the cohort showed that: i) none were deficient in selenium (with plasma selenium levels less than 80 ppb); ii) the cohort average plasma selenium level, 141 ppb, was slightly greater than that of the NHANES-III cohort; iii) plasma selenium level was positively associated with the consumption of dairy products, fish, and fish other than tuna, as estimated from food frequency questionnaire methodology; and iv) individuals with the Leu/Leu genotype for extracellular glutathione peroxidase constituted 11% of the cohort and had plasma selenium levels ca. 10% lower that the cohort average. ADODR monitoring activities to evaluate and discuss the research progress included teleconferences and electronic mail correspondence.