This project is directed toward the isolation, identification, and characterization of certain mycotoxins and toxins that represent either normal or stress metabolites of food plants. Novel tremorgenic myotoxins recently detected in hay or forage samples from bovine neurological disease outbreaks will be bioproduced in laboratory cultures, isolated, and identified as to chemical structure. Their toxicological properties will be compared with other mycotremorgens. Other available tremorgens will be characterized in regard to their neuropharmacological, biochemical, and pathological activities in animals including sub-human primates dosed at various levels over different time periods. Search will continue for the toxic principle (metabolite) of Fusarium moniliforme shown to be responsible for a disease in equines known as leucoencephalomalacia. Specifically, a recently discovered but unidentified toxin of this organism will be tested in equines. Attempts will be made to isolate the toxin in pure form and to characterize it chemically and toxicologically. Toxins of higher plants to receive attention include lung-toxic stress metabolites of the sweet potato, especially-4ipomeanol, and a prominent lung toxic component of perilla mint plant, perilla ketone. Radioactive perilla ketone will be prepared and compared with 4-ipomeanol as regards bioactivation and covalent binding to target cell macromolecules. Plans also call for using these toxins in an elaborate experimental system which measures pulmonary hemodynamics, arterial blood gases, and lung lymph flow in chronically instrumental, unanesthetized sheep. The biological sources of all the above naturally occurring toxins are plants that are often ingested by livestock and also may serve as sources of human foods. The toxins, however, may prove even more important to human biology and medicine as tools for investigating both normal and pathological processes, thereby contributing indirectly to human welfare.
