Sphingolipids are found in significant amounts in food; however, little is known about their nutritional significance. Sphingomyelin (SM) is digested to ceramides and sphingoid bases (which can modulate cell growth, differentiation, and apoptosis), and the feeding of SM to female CF1 mice treated with N,N-dimethylhydrazine (DMH) reduced the number of aberrant colonic crypt foci and adenocarcinomas. Therefore, dietary SM appears to be an important component of food. This proposal will conduct the first analyses of the nutritional significance of the other major category of sphingolipids glyco- sphingolipids (GSL). A common GSL of plants (cerebrosides) will be purified and characterized, then fed to CF1 mice to determine its effect on DMH-induced colon carcinogenesis. Based on preliminary data, plant cerebrosides will be even more potent than SM in inhibiting colon carcinogenesis; therefore, the mechanisms for their effects will be explored at two levels: 1) characterization of the digestion of GSL and their delivery to the colon; and, 2) analysis of the cellular effects of the metabolites of GSL (ceramides, sphingoid bases, and psychosines). The latter studies will also be conducted with GSL from other plants to provide a better understanding of the structure-function relationships between the different types of sphingolipids in food and their potential biological effects. These studies could lead to a better understanding of the relationships between diet and cancer through identification of glycosphingolipids as important constituents of food.
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