The aim of the present study was to examine whether crude glycosphingolipid (cGSL) has short-term chemopreventive effects on the preneoplastic biomarker lesions involved in carcinogen-induced rat colon carcinogenesis. We also examined whether cGSL affects cell proliferation and apoptosis in these lesions. The crude preparation was obtained by the simple ethanol extraction method. Five-week-old male F344 rats were divided into 6 groups. Rats in groups 1-4 were given subcutaneous injections of azoxymethane (AOM) (20 mg/kg body weight) once a week for 2 weeks. Starting 1 week before the first injection of AOM, the rats in groups 2, 3 and 4 were fed a diet containing 250, 1,000 and 3,000 ppm cGSL, respectively, for 5 weeks. The experiment was terminated 5 weeks after the start date, and the number of aberrant crypt foci (ACF) and mucin-depleted foci (MDF) was counted. Dietary cGSL significantly inhibited the induction of ACF (group 3, P<0.01; group 4, P<0.05) and MDF (groups 2 and 3, P<0.001; group 4, P<0.05) as compared to group 1 treated with AOM alone. In groups 3 and 4, proliferating cell nuclear antigen-positive indices of epithelial cells were significantly lower than in group 1 (group 3, P<0.05; group 4, P<0.005). Caspase-3-positive indices were significantly higher in groups 3 and 4 than in group 1 (group 3, P<0.01; group 4, P<0.001). These results suggest that dietary cGSL had a potent chemopreventive effect in the present short-term colon carcinogenesis bioassays, and that this effect may be associated with the inhibition of ACF and MDF and the induction of apoptosis.

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