SPHINGOMYELIN CONSUMPTION SUPPRESSES ABERRANT COLONIC CRYPT FOCI AND INCREASES THE PROPORTION OF ADENOMAS VERSUS ADENOCARCINOMAS IN CF1 MICE TREATED WITH 1,2-DIMETHYLHYDRAZINE - IMPLICATIONS FOR DIETARY SPHINGOLIPIDS AND COLON CARCINOGENESIS

Sphingolipids are hydrolyzed in the gastrointestinal tract to ceramide , sphingosine, and other metabolites that can modulate cell growth, di fferentiation, and apoptosis. To characterize the effects of dietary s phingolipids on colon carcinogenesis, female CF1 mice were administere d 1,2-dimethylhydrazine and then fed an essentially sphingolipid-free diet supplemented with 0 to 0.1% (w/w) sphingomyelin (SM) purified fro m milk. As was found in a previous pilot study (D. L. Dillehay et al., J. Nutr., 124: 615-620, 1993), SM (@ 0.1%) reduced the number of aber rant colonic crypt foci (by 70%, P < 0.001) and aberrant crypts per fo cus (by 30%, P < 0.003), which are early indicators of colon carcinoge nesis. In longer term studies, SM had no effect on colon tumor inciden ce or multiplicity; however, up to 31% of the tumors of mice fed SM we re adenomas, whereas all of the tumors of mice fed the diet without SM mere adenocarcinomas. These findings demonstrate that milli SM suppre sses the appearance of more advanced, malignant tumors as well as earl y markers of colon carcinogenesis. Although the sphingolipid content o f foods has not been widely studied, several foods (e.g., milk and soy beans) contain the sphingolipid levels used in these investigations; t herefore, this class of compounds could be significant contributors to the cancer preventive effects of some foods.