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Cytokeratin, Lectin, and Acidic Mucin Modulation in Differentiating Colonic Epithelial Cells of Mice after Feeding Western-style Diets¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [K. Y., K. F., H. N., D. L., M. L.]; Strang Cancer Prevention Center, New York, New York 10021 [K. Y., K. F., H. N., M. L.]; and Chemoprevention Branch, Cancer Research Program, Division of Cancer Prevention and Control, National Cancer Institute, NIH, Bethesda, Maryland 20892 [V. E. S., G. J. K.]

Several studies have recently reported the development of colonic epithelial cell hyperproliferation in rodents following the ingestion of Western-style diets. In this study, additional measurements related to differentiation and maturation of the colonic epitheial cells were made after feeding this type of diet. Two Western-style diets high in fat and phosphate content and low in calcium and vitamin D were fed to C57BL/6J mice for 12, 24, and 52 weeks. Diet A contained American Blend fat as a source of lipids, diet B contained corn oil, and control diet C was a standard AIN-76A semisynthetic diet which is lower in fat content and higher in calcium and vitamin D. Colonic epithelial cells were studied for three biomarkers: cytokeratin catalogue no. 18 (clone LE64) expression, soybean agglutinin carbohydrate lectin binding, and acidic mucins including sialo- and sulfomucins. Feeding of diets A and B revealed that colonic epithelial cells had increased expression of cytokeratin catalogue 18 and SBA carbohydrate lectin binding compared to controls (P = 0.0001 for diet A versus C and diet B versus C). Significant differences were found between diets B and C (P = 0.0001) and diets A and C (P = 0.0001) in total acidic mucins and in the ratio of sialomucin:sulfomucin (P = 0.0001). These findings demonstrate that both functional and structural modifications occurred in colonic epithelial cells under these dietary conditions, and further defined this rodent model for preclinical evaluation of nutritional and chemopreventive interventions.

¹ This study was supported by National Cancer Award NO1-CN-25498 and the National Dairy Research and Promotion Board.

² To whom requests for reprints should be addressed, at Strang Cancer Research Laboratory, Rockefeller University, Box 287, 1230 York Avenue, New York, NY 10021.

Received 11/16/95. Accepted 8/15/96.

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