Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium

High intake of red meat is associated with increased colon cancer risk. We have shown earlier that this may be due to the high haem content of red mea t, because dietary haem increased cytolytic activity of faecal water and co lonic epithelial proliferation. Dietary calcium inhibits diet-induced epith elial hyperproliferation. Furthermore, it has been shown that supplemental calcium inhibited the recurrence of colorectal adenomas. Therefore, we stud ied whether dietary calcium phosphate can exert its protective effects by i nhibiting the deleterious effects of haem. In vitro, calcium phosphate prec ipitated haem and inhibited the haem-induced cytotoxicity. Subsequently, ra ts were fed diets, differing in haem (0 or 1.3 mu mol/g) and calcium phosph ate content only (20 or 180 mu mol/g). Faeces were collected for biochemica l analyses. Cytolytic activity of faecal water was determined from the degr ee of lysis of erythrocytes by faecal water. Calonic epithelial proliferati on was measured in vivo using [H-3]thymidine incorporation. In rats fed low calcium diets, dietary haem increased cytolytic activity of faecal water ( 98 +/- 1 versus 1 +/- 1 %, P < 0.001) and the concentration of cations in f aeces (964 +/- 31 versus 254 +/- 20 mu mol/g), when compared with controls. This indicates that dietary haem increased colonic mucosal exposure to lum inal irritants. Colonic epithelial proliferation was increased compared wit h controls (70 +/- 4 versus 48 +/- 8 d.p.m./mug DNA, P < 0.001). This was a ccompanied by metabolism of the ingested haem and solubilization of haem co mpounds in the faecal water. A high calcium diet largely prevented this met abolism and solubilization. It also inhibited the haem-induced cytolytic ac tivity of faecal water and increase in faecal cation concentration. In acco rdance, the haem-induced colonic epithelial hyperproliferation was prevente d. We therefore suggest that dietary calcium phosphate acts as a chemopreve ntive agent in colon carcinogenesis by inhibiting the cytolytic and hyperpr oliferative effects of dietary haem.