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Sphingolipids display a wide spectrum of biological activities, including cell growth, differentiation and apoptosis. However, precise mechanisms by which these compounds exert anticancer or cancer-preventive effects are not known. In the present study, we evaluated the preventive efficacy of enriched dietary monoglucosylceramide 1-O-β β β β-glucosyl-N-2′ ′ ′ ′-hydroxyarachidoyl-4,8-sphingadienine (G 1 CM) on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) and β β β β-catenin-accumulated crypt (BCAC) formation in F344 rats during initiation stage. We also examined whether G 1 CM affects cell proliferation and apoptosis in these lesions. Pure G 1 CM was isolated from rice bran. Forty-two rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneous injections of DMH (40 mg/kg body weight) once a week for 2 weeks. One week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 200 and 1000 p.p.m. G 1 CM, respectively, for 5 weeks. Rats in group 4 were fed a diet containing 1000 p.p.m. G 1 CM. Rats in group 5 were given the basal diet alone and served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary G 1 CM at both doses (groups 2 and 3) significantly inhibited the induction of ACF and BCAC (P < 0.001) when compared to group 1 treated with DMH alone. In groups 2 and 3, the proliferating cell nuclear antigen labeling indices of epithelial cells in ACF and BCAC were also lower than in group 1 (P < 0.0001 for ACF, P < 0.05 for BCAC).

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