RELATIONSHIP AMONG COLONOCYTE PROLIFERATION, DIFFERENTIATION, AND APOPTOSIS AS A FUNCTION OF DIET AND CARCINOGEN

To determine the relationship among colonocyte proliferation, differen tiation, and apoptosis as a function of fiber and carcinogen, we condu cted a 2 X 2 factorial design study with two fibers (pectin or cellulo se) and two injection protocols (azoxymethane or saline) in male Sprag ue-Dawley rats. Rats were killed six weeks after the injections, and i n vivo cell proliferation was measured by incorporation of bromodeoxyu ridine into DNA, differentiation by binding of the lectin Dolichos bif lorus agglutinin, and apoptosis by immunoperoxide detection of digoxig enin-labeled genomic DNA. In the proximal colon, pectin decreased diff erentiated and apoptosis, resulting in a greater number of cells per c rypt column. In the distal colon, pectin increased cell proliferation, resulting in more crypts per millimeter of colon and a greater number of surface cells. Azoxymethane increased cell proliferation and decre ased differentiation and apoptosis in the proximal and the distal colo n. This resulted in a greater number of surface cells proximally and m ore crypts per millimeter of colon distally. These results illustrate the importance of considering all three parameters (proliferation, dif ferentiation, and apoptosis) when evaluating neoplastic growth.