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Premalignant Alterations in the Glycosphingolipid Composition of Colonic Epithelial Cells of Rats Treated with 1,2-Dimethylhydrazine¹

Departments of Medicine, Michael Reese Hospital [R. D., P. K. D., T. A. B.], and University of Chicago Hospitals and Clinics [T. A. B.], Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637

1,2-Dimethylhydrazine is a procarcinogen with selectivity for the colon. In weekly s.c. doses of 20 mg/kg of body weight, this agent produces colonic tumors in virtually 100% of rodents, with a latency period of approximately 6 months. To determine whether alterations in the glycosphingolipid content and composition of rat colonic epithelial cells existed before the development of dimethylhydrazine-induced colon cancer, rats were given s.c. injections of this agent (20 mg/kg body weight per week) or diluent for 5 weeks. Animals were sacrificed at this time period and colonocytes isolated from each group. Glycosphingolipids were then extracted from these cells and analyzed by thin-layer chromatography, high-performance liquid chromatography and gas-liquid chromatography.

The results of these studies demonstrate that: (a) the content and relative percentages of globotriaosylceramide is increased, whereas hematoside and globotetraosylceramide are decreased in dimethylhydrazine-treated colonocytes compared to their control counterparts; and (b) differences in the enzymatic activities responsible for the biosynthesis of these glycosphingolipids appear to explain, at least partially, these compositional differences. The present data, therefore, suggest that alterations in certain glycosphingolipids may be an early event in colonic malignant transformation and, furthermore, that these alterations may prove useful in the detection of early colon cancer.

¹ This investigation was supported by CA36745 awarded by the National Cancer Institute.

² Recipient of a Merit Award from the National Cancer Institute, NIH. To whom requests for reprints should be addressed, at Section of Gastroenterology, University of Chicago Hospitals and Clinics, Box 400, 5841 South Maryland Avenue, Chicago, IL 60637.

Received 5/ 5/86. Revised 11/17/86. Accepted 11/18/86.

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