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perimental colon carcinoma in mice, indicating that the abnormal metabolism of sphingomyelin is linked to colon carcinoma development. However, the changes 1 Department of Medicine, Lund University Hospital, Lund, Sweden.in sphingomyelinase (SMase) activity in colon carcinoma have not been directly studied. The authors identified, specifically in the intestine, a distinctive alkaline 2 Research Park Ideon, Swedish Dairies AssociSMase that differs from the known acidic and neutral SMases. The functions and ation, Lund, Sweden.clinical implications of the enzyme are unknown. This study examined the changes 3 Department of Cell Biology, Lund University in all three SMase activities in human colorectal carcinoma. Hospital; Lund, Sweden. METHODS.Tissue samples were taken from colorectal carcinoma and normal mucosa from 18 patients. After homogenization, the activities of acidic, neutral, and alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined. The enzyme activities in cancer tissue were compared with normal tissue from the same patients. RESULTS.In the normal tissue, there is an activity gradient from the ascending colon to the rectum for neutral and alkaline SMases but not for acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and 50%, respectively. No changes could be found for either ceramidase or alkaline phosphatase activity. CONCLUSIONS.Alkaline SMase activity preferentially decreases in human colorectal carcinoma, suggesting a regulatory role of the enzyme in colon mucosa cell proliferation.