DIETARY-FAT AND FIBER ALTER RAT COLONIC PROTEIN-KINASE-C ISOZYME EXPRESSION

To better understand the biochemical mechanisms by which select fats a nd fibers modulate colonic cell proliferation, we determined the profi le of protein kinase C (PKC) isozymes and cell proliferation in rat pr oximal and distal colonic mucosa following diet manipulation, because enhanced cell proliferation has been correlated with colon cancer inci dence. Rats were assigned to one of four diets (each with 15 g fat + 6 g fiber/100 g diet) for 3 wk: fiber-free fish oil (FF), fiber-free co rn oil (FC), cellulose + corn oil (CC), or pectin + corn oil (PC). Ste ady-state levels of colonic mucosal cytosolic and membrane PKC isozyme s were determined. In vivo cell proliferation was determined by bromod eoxyuridine incorporation into DNA. In addition, viable exfoliated col onic epithelial cells were isolated from feces using Percoll bovine se rum albumin gradients. We found that 1) proximal and distal colonic mu cosa possessed different steady-state levels and relative proportions of PKC isozymes; 2) PKC alpha and delta expression were significantly greater in distal membrane of the PC-fed group compared with the other dietary groups; 3) the number of exfoliated cells per 4-h fecal colle ction generally was proportional to the diet-induced changes in cell p roliferation (PC>FC>CC>FF). These data demonstrate that dietary treatm ent altered colonic PKC isozyme expression, with animals fed the fiber -containing diets generally expressing higher steady-state levels of P KC alpha and delta.