DIETARY SPHINGOMYELIN INHIBITS 1,2-DIMETHYLHYDRAZINE-INDUCED COLON-CANCER IN CF1 MICE

Sphingolipids are in all eukaryotic cells and modulate cell growth, di fferentiation, and transformation; however, little is known about the physiological effects of their consumption. Mice were fed diets supple mented with milk sphingomyelin to determine effects on colon carcinoge nesis. Cancer was initiated in CF1 mice by 1,2-dimethylhydrazine. Mice were then fed AIN76A diets supplemented with 0.025 to 0.1 g sphingomy elin/100 g for 28 wk until the supply of sphingomyelin was depleted an d then fed unsupplemented diet for 24 wk. Sphingomyelin did not affect weight gain. Mice fed sphingomyelin had a 20% incidence of colon tumo rs compared with 47% in controls (P = 0.08 for all sphingomyelin-fed m ice vs. controls). Tumors were adenomas or adenocarcinomas and located in the distal third of the colon. In shorter-term studies, colonic ep ithelial cell proliferation was significantly greater than controls in mice fed 0.025 g sphingomyelin/100 g diet, but not in those fed highe r amounts of sphingomyelin. The number of aberrant crypts was signific antly lower in 1,2-dimethylhydrazine-treated mice fed 0.05 g sphingomy elin/100 g diet than in controls. These results demonstrate that consu mption of sphingomyelin affects the behavior of colonic cells. Because sphingolipids are present in food, the reduction in 1,2-dimethylhydra zine-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.