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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 Carcinogenesis¹

Departments of Biochemistry [E. M. S., A. H. M.], Pathology [D. L. D.], and Chemistry and the Emory Mass Spectrometry Center [A. R., J. A.], and Division of Animal Resources [D. L. D., S. K. W.], Emory University, Atlanta, Georgia 30322

Sphingolipids are hydrolyzed in the gastrointestinal tract to ceramide, sphingosine, and other metabolites that can modulate cell growth, differentiation, and apoptosis. To characterize the effects of dietary sphingolipids on colon carcinogenesis, female CF1 mice were administered 1,2-dimethylhydrazine and then fed an essentially sphingolipid-free diet supplemented with 0 to 0.1% (w/w) sphingomyelin (SM) purified from milk. As was found in a previous pilot study (D. L. Dillehay et al., J. Nutr., 124: 615–620, 1994), SM (@ 0.1%) reduced the number of aberrant colonic crypt foci (by 70%, P < 0.001) and aberrant crypts per focus (by 30%, P < 0.003), which are early indicators of colon carcinogenesis. In longer term studies, SM had no effect on colon tumor incidence or multiplicity; however, up to 31% of the tumors of mice fed SM were adenomas, whereas all of the tumors of mice fed the diet without SM were adenocarcinomas. These findings demonstrate that milk SM suppresses the appearance of more advanced, malignant tumors as well as early markers of colon carcinogenesis. Although the sphingolipid content of foods has not been widely studied, several foods (e.g., milk and soybeans) contain the sphingolipid levels used in these investigations; therefore, this class of compounds could be significant contributors to the cancer preventive effects of some foods.

¹ Supported by funds from the National Dairy Board administered in cooperation with the National Dairy Council and National Cancer Institute Grant CA61820.

² To whom requests for reprints should be addressed, at Department of Biochemistry, 4113 Rollins Research Center, Emory University, Atlanta, GA 30322. Phone: (404) 727-5978; Fax: (404) 727-3954.

Received 7/ 2/96. Accepted 9/ 3/96.

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