COLONIC EPITHELIAL-CELL PROLIFERATION IN A RAT MODEL OF NONGENOTOXIN-INDUCED COLONIC NEOPLASIA

BACKGROUND: The effect on colonic cell proliferation of poligeenan, a nongenotoxic polysaccharide that induces colon tumors in rats, was compared with guar gum and carrageenan. EXPERIMENTAL DESIGN: Fischer 344 rats were fed a basal diet supplemented with carrageenan and poligeenan fibers for up to 91 days. The quantitative levels of proliferation, location of the proliferating cells, and the ability of the mucosa to readapt by removing the experimental fibers from the diet were tested. RESULTS: The mucosal epithelium exhibited a 5-fold increase in thymidine kinase activity in both the carrageenan and poligeenan groups. Proliferating cells appeared at the luminal surface only in the poligeenan-treated rats, and the number of proliferating cells in the upper third of the crypt increased 35-fold. A second and third set of animals were fed one of the three test diets for either 28 or 64 days, followed by a 28-day recovery period. Proliferation in the guar- and carrageenan-treated groups returned to basal levels. In poligeenan-treated rats, thymidine kinase levels, and proliferating cells in the upper third of the crypt remained 2- and 11-fold, respectively, above controls. CONCLUSIONS: The difference in recovery time between the poligeenan group and the others, and the luminal location of proliferating cells may prove useful as markers in understanding early events in the carcinogenic process induced by a nongenotoxin.