Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced colon cancer in CF1 mice.
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.
Dillehay
D L
DL
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322-3050.
Webb
S K
SK
Schmelz
E M
EM
Merrill
A H
AH
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002828:Choristoma / Q000139:chemically induced; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004127:Dimethylhydrazines / Q000633:toxicity; D005260:Female; D051379:Mice; D013109:Sphingomyelins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
D002273:Carcinogens; D004127:Dimethylhydrazines; D013109:Sphingomyelins; D019813:1,2-Dimethylhydrazine