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Dietary Sphingomyelin Inhibits 1,2-Dimethylhydrazine-Induced Colon Cancer in CF1 Mice^1,2,3,4,

Dirck L. Dillehay⁵, Sonji K. Webb^*, Eva-Maria Schmelz and Alfred H. Merrill, Jr.

Department of Pathology ^* Division of Animal Resources, Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322-3050

Sphingolipids are in all eukaryotic cells and modulate cell growth, differentiation, and transformation; however, little is known about the physiological effects of their consumption. Mice were fed diets supplemented with milk sphingomyelin to determine effects on colon carcinogenesis. Cancer was initiated in CF1 mice by 1,2-dimethylhydrazine. Mice were then fed AIN76A diets supplemented with 0.025 to 0.1 g sphingomyelin/100 g for 28 wk until the supply of sphingomyelin was depleted and then fed unsupplemented diet for 24 wk. Sphingomyelin did not affect weight gain. Mice fed sphingomyelin had a 20% incidence of colon tumors compared with 47% in controls (P = 0.08 for all sphingomyelin-fed mice vs. controls). Tumors were adenomas or adenocarcinomas and located in the distal third of the colon. In shorter-term studies, colonic epithelial cell proliferation was significantly greater than controls in mice fed 0.025 g sphingomyelin/100 g diet, but not in those fed higher amounts of sphingomyelin. The number of aberrant crypts was significantly lower in 1,2-dimethylhydrazine-treated mice fed 0.05 g sphingomyelin/100 g diet than in controls. These results demonstrate that consumption of sphingomyelin affects the behavior of colonic cells. Because sphingolipids are present in food, the reduction in 1,2-dimethylhydrazine-induced premalignant lesions and the incidence of colon tumors in CF1 mice implies that these compounds may be another important class of nutritional modulators of carcinogenesis.

KEY WORDS: • sphingomyelin • colon cancer • aberrant crypts • cell proliferation • mice

¹ Portions of this study were presented at the Annual Meeting of the Federation of American Societies for Experimental Biology, April 1993, New Orleans, LA [Dillehay, D. L., Crall, K. J., Webb, S. K., Schmelz, E. & Merrill, A. H., Jr. (1993) Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced colon cancer in CF1 mice. FASEB J. 7: A398 (abs.)].

² Supported by funds from the American Cancer Society grant IRG-182 and National Dairy Board and administered in cooperation with the National Dairy Council.

³ Dedicated to the memory of Allene T. Merrill.

⁴ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁵ To whom correspondence and reprint requests should be addressed at: Rollins Research Center, G70, Emory University School of Medicine, Atlanta, GA 30322-3050.

Manuscript received 23 July 1993. Revision accepted 12 November 1993.

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