INCREASES IN THE CONCENTRATIONS OF AVAILABLE IRON IN RESPONSE TO DIETARY IRON SUPPLEMENTATION ARE ASSOCIATED WITH CHANGES IN CRYPT CELL-PROLIFERATION IN RAT LARGE-INTESTINE

High concentrations of iron in the diet have been shown to increase ch emically induced colorectal tumors in rats. It is therefore important to understand the influence of dietary iron on the concentration of un absorbed iron in the large intestine and its distribution between solu ble and insoluble pools in the luminal compartment. We sought to inves tigate this issue and to establish whether iron modifies mucosal cell proliferation, which is thought to influence initiation and progressio n through the adenoma carcinoma sequence. in the first experiment, fou r groups of seven rats were fed diets at two concentrations of iron, 2 9 and 102 mg/kg, with or without the addition of 2.5 g phytic acid/kg. The concentrations of iron in the contents of the large bowel extract able with water (''free iron'') or a buffered EDTA solution (''exchang eable iron'') were determined, The concentration of freely soluble iro n increased similar to 100% with iron supplementation in both the cecu m and the colon, and there was an approximately five-to sixfold increa se in exchangeable iron at both sites (P < 0.05), In a second experime nt with identical feeding conditions, there was a significantly greate r number of cell divisions per crypt in the colon of the high iron gro up and a significantly greater number of cell divisions in the upper p art of the crypt in the cecum. The concentrations of free and exchange able iron observed in colonic contents in this study are consistent wi th those reported by others to increase free radical production in fec al material. Further studies are required to determine whether the sma ll changes in crypt cytokinetics are a consequence of oxidative mucosa l damage.