Task 1. Fish Research. Extend prior experimental test tube evidence by using live models (Rainbow Trout) to determine the effect on cancer resistance of those parameters that were found to increase the PUFA dependant catalase to peroxidase ratio in the test tube.* Some of the factors that in reasonable physiological concentrations increased this ratio were ascorbic acid and alpha tocopherol. Retinol acetate to a much lessor extend had a similar effect. However because of other evidence** both retinol esters and retinoic acid are being included along with ascorbic acid and alpha tocopherol in this phase of the of our research. Then extend the same queries and tests to other types of cancer. CLICK ON CURRENT RESULTS TO SEE CURRENT STATUS AND RESULTS TO DATE.

Task 2. Other Species. Confirm whether past experiments, that show a correlation of hepatoma susceptibility to the deficiency of the detoxifying catalase enzyme found in certain fish species, is a phenomenon that occurs repeatedly or generally in cancer susceptible species. And further, determine whether the low activity of PUFA dependant catalase is actually causative or is only coincidental and unrelated to carcinogenesis.

Task 3. Gene Receptors. Determine if the development of tumors in trout liver and in other locations and animals is related to a dysfunction of certain gene receptors. Of particular concern are the receptors which activate transcription for proteins effecting cell differentiation.** This phase of the research will target the events and metabolism surrounding the retinoid receptors - trans retinoic acid receptors (RAR) and 9-cis retinoic acid receptors (RXR). The object is to find whether inhibited cell differentiation is related to depressed formation of specific retinoids which are necessary for activating either RAR or RXR, or to a dysfunction of retinoid binding (carrier) proteins or to other factors in this chain which regulates transcription.

Task 4. Cell Controls. Determine whether the previously demonstrated PUFA dependant catalase is involved in the metabolic pathways which ultimately control cell differentiation, cell growth and cell death.

Task 5. Cell Culture. In cell cultures compare hepatoma and non hepatoma cells in rainbow trout with the hepatoma resistant cells of other salmonid fish.

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* See the "MISSION STATEMENT" and its attached description of the polyunsaturated fatty acid dependent catalase mediated oxidation of organic molecules entitled "Catalase Deficiency and Hepatoma Susceptibility in Steelhead Trout".

** See the following articles reviewing recent research with retinol and retinoic acid.

"The Retinol-Binding Protein Superfamily", by A. Sivaprasadarao and J. B. C. Findlay Chap. 4 in: Vitamin A in Health and Disease, Ed. By Rune Blomhoff; 1994, Marcel Deckker, Inc.

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