An endogenous colon mitosis inhibitor reduces the increased cell proliferation in colonic epithelium induced by dietary cholic acid and treatment with 1,2-dimethylhydrazine

We have recently purified and identified a tripeptide (pGlu-His-GlyOH)in mouse intestinal extracts which reversibly inhibits normalcolonic epithelial cell renewal in mice. We also found a similarresponse to a single injection of the peptide during bile-acid-inducedhyperproliferation in the colonic epithelium. To investigatethe effect of repeated injections of the same dose of the inhibitorunder various pathological conditions of the colonic mucosawe either fed mice low-calcium cholic acid diet, treated theanimals with a single injection of the colon carcinogen 1,2-dimethyl-hydrazine(DMH), or gave both treatments. The peptide reduced the mitoticrate and the labelling indices in the colonic epithelium duringthe first 5 days of feeding the low-calcium cholic acid diet,and the size of the proliferative compartment was reduced. Proliferatingcells were found significantly closer to the base of the crypisin the peptide-treated animals. The mitotic rate was also reducedby each of repeated peptide injections during the first 72 hin the DMH-treated animals; the labelling indices at 48 and72 h only. By feeding DMH-treated animals low-calcium cholicacid diet, similar results were obtained. However, in all carcinogen-treatedanimals the tripeptide had no effect on the size and localizationof the proliferating cells in the colonic crypts.