Effects of Calcium and Bile Acid Feeding on Colon Tumors in the Rat

The hypothesis that dietary calcium alters the incidence of colorectal neoplasms was examined in an established model of carcinogenesis. Male Fischer 344 rats (28 days old) were quarantined for 2 weeks. All animals were fed the basal diet (AIN-76) supplemented with cholic acid (0.2%) and/or calcium (1.6%, corresponding to a 3-fold increase above that of the basal diet). N -Methyl- N -nitrosourea (MNU) (2 mg/dose) or saline (control) was given intrarectally to all animals on days 1 and 4 of the experiment. Groups 1–8 were fed the experimental diets concurrently with the first dose of MNU, while groups 9 and 10 were fed the diets 2 weeks prior to MNU (or saline). All animals were sacrificed after 28 weeks. No tumors were observed in the groups given saline (groups 1, 3, 5, 7, and 9). In groups receiving MNU, the addition of cholic acid to the diet (group 4) caused a significant increase in tumors (80% versus 55%), tumors/animal ratio (2.24 versus 0.75), and tumors/tumor-bearing animal ratio (2.80 versus 1.36), group 4 versus group 2, respectively. Increased dietary calcium did not inhibit tumor formation; 68% of animals in groups 6 and 10 had tumors. The combination of dietary cholic acid and calcium (group 8) gave a tumor incidence similar to cholic acid (group 4) alone (72% versus 80%, 2.00 versus 2.24 tumors/animal; 2.77 versus 2.80 tumors/tumor-bearing animal). Most tumors were adenomatous polyps but carcinomas in situ and invasive carcinomas were also present; dietary calcium reduced the number of invasive carcinomas (group 6 versus group 2, P < 0.04).