Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium

High intake of red meat is associated with an increased risk of colon cance r. It has been suggested that fat from red meat is responsible, because hig h fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role fbr fat, however. Recently, we showed that dietary haem, which is abundant in red me at, increased colonic cytotoxicity and epithelial proliferation. In this st udy, we wanted to clarify whether dietary fat affects colon cancer risk by itself or by modulating the detrimental effects of haem on the colonic epit helium. Rats were fed control or haem-supplemented diets with 10%, 25% or 4 0% of the energy derived from fat for 14 days. Faeces were collected for bi ochemical analyses. Colonic cytotoxicity was determined from the degree of lysis of erythrocytes by faecal water: Colonic epithelial proliferation was measured in vivo using [H-3]thiymidine incorporation. Increasing the fat c ontent of the control diets stimulated faecal disposal of both fatty acids and bile acids. It also increased the concentration of fatty acids, but not that of bile acids, in faecal water in control rats. The cytolytic activit y of faecal water and colonic epithelial proliferation were unaffected. Die tary haem increased faecal cation content and cytolytic activity of faecal water at all fat levels, suggesting that the colonic mucosa was exposed to high amounts of luminal irritants. This effect was smaller in rats on the l ow-fat diet. Dietary haem also increased colonic epithelial proliferation a t;all fat levels. The haem-induced effects were independent of fatty acids or bile acids in the faecal water. In western societies, 30-40% of ingested energy is supplied by dietary fat, so our results suggest that the associa tion between consumption of red meat and risk of colon cancer is mainly due to its haem content, and is largely independent of dietary fat content.