Beef meat and blood sausage promote azoxymethane - induced 1 mucin - depleted foci and aberrant crypt foci in rat colons

16 dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromid, TBARS: thiobarbituric acid reactive 17 substances 18 4-Data were presented at the 4 th Abstract 23 24 Red meat is associated with colon cancer risk. Puzzlingly, meat does not promote 25 carcinogenesis in rodent studies. However, we demonstrated previously that dietary heme 26 promotes aberrant crypt foci (ACF), in rats given a low-calcium diet. Here, we test the 27 hypothesis that heme-rich meats promote colon carcinogenesis in rats treated with 28 azoxymethane, in low-calcium diets (20 mmol/kg). Three meat diets were formulated to 29 contain varying concentrations of heme by the addition of raw chicken, beef, or black 30 pudding (blood sausage). The no-heme control diet was supplemented with ferric citrate, and 31 a heme control diet with hemoglobin, to match iron or heme concentration in the beef diet. 32 After 100 d colons were scored for ACF and mucin-depleted foci (MDF). Fecal water was 33 assayed for lipoperoxides and cytotoxicity. Only diets with heme promoted MDF, but all 34 meat diets promoted ACF. The number of MDF/colon was 0.550.68 in controls, but 1.2±0.6 35 (p=0.13), 1.9±1.4 (p<0.01) and 3.0±1.2 (p<0.001) in chicken, beef and black pudding-fed 36 rats. MDF promotion was significantly greater for the high-heme black pudding diet, than for 37 the median-heme beef diet. The number of ACF/colon was 71±16 in controls, but 90±18, 38 99±13 and 103±14 in chicken, beef, and black pudding-fed rats (all p<0.001). No ACF or 39 MDF difference was seen between beef and the matching heme control diet. MDF promotion 40 correlated with high fecal water lipoperoxides and cytotoxicity (r=0.65, p<0.01). This is the 41 first study to show the promotion of experimental carcinogenesis by dietary meat, and the 42 association with heme intake.