The specific objectives of the proposed research are to determine the chemical compounds of selenium deposited in tissues as influenced by the administered forms using both tissue cultures and the live animal, to study the induction of selenoproteins by selenium, and to investigate the influence of selenium deficiency on immunity. Radioactive selenite, selcnomethionine and selenocystine will be administered to rats and lambs, and the chemical forms present in intestinal contents, intestinal mucosa, blood and liver determined. The metabolic changes occurring in these selenium compounds are planned to be determined by intestinal perfusion techniques, cannulation of the mesenteric and portal veins, and in vitro incubations of intestinal contents, mucosa cells and tissue cellular fractions. Tissue cultures are planned to determine selenium requirements of, the uptake and incorporation of, and the chemical forms when fibroblasts are grown with selenite, selenomethionine or selenocystine. Chromatography on ion exchange resin columns and gel filtration methods are planned techniques to determine the chemical forms of selenium. Since most of the selenium is present as organic compounds in plants, but selenite has been used to treat deficiencies it is important to obtain more information on metabolism of various selenium containing compounds. Selenium will be injected into selenium deficient rats and lambs, and the relative rates of synthesis of the selenoproteins measured by gel filtration of tissue cytosols at various times afterwards. The use of protein inhibitors is planned to determine whether protein synthesis is necessary for selenium incorporation into these proteins. In further studies, rats are planned to be fed various levels of dietary selenium and the deposition of selenium in cytosolic proteins determined by gel filtration. The immunity studies are planned with sheep using in vivo antibody response to bovine viral diarrhea virus vaccine, and with mitogen-induced lymphocyte blastogenesis in vitro, a test of the functional capacity of the immune system. An understanding of the metabolism of various selenium compounds will be valuable for assessing the implications of this element in human health.
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