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 normal colonic epithelial cell renewal in mice. We also found a similar response to a single injection of the peptide during bile-acid-induced hyperproliferation in the colonic epithelium. To investigate the effect of repeated injections of the same dose of the inhibitor under various pathological conditions of the colonic mucosa we either fed mice low-calcium cholic acid diet, treated the animals with a single injection of the colon carcinogen 1,2-dimethylhydrazine (DMH), or gave both treatments. The peptide reduced the mitotic rate and the labelling indices in the colonic epithelium during the first 5 days of feeding the low-calcium cholic acid diet, and the size of the proliferative compartment was reduced. Proliferating cells were found significantly closer to the base of the crypts in the peptide-treated animals. The mitotic rate was also reduced by each of repeated peptide injections during the first 72 h in the DMH-treated animals; the labelling indices at 48 and 72 h only. By feeding DMH-treated animals low-calcium cholic acid diet, similar results were obtained. However, in all carcinogen-treated animals the tripeptide had no effect on the size and localization of the proliferating cells in the colonic crypts.
Skraastad
O
O
Institute of Pathology, Rikshospitalet, Oslo, Norway.
Reichelt
K L
KL
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002118:Calcium / Q000502:physiology; D002455:Cell Division / Q000187:drug effects*; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D003106:Colon / Q000166:cytology* / Q000187:drug effects; D004032:Diet; D004127:Dimethylhydrazines / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology; D008763:Methylhydrazines / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives
D002793:Cholic Acids; D004127:Dimethylhydrazines; D006131:Growth Inhibitors; D008763:Methylhydrazines; D009842:Oligopeptides; C023866:pyroglutamyl-histidyl-glycine; D019826:Cholic Acid; D019813:1,2-Dimethylhydrazine; D002118:Calcium; D011761:Pyrrolidonecarboxylic Acid