Maintenance of the colonic epithelial is regulated by small changes in proliferation and apoptosis and is affected by fiber and carcinogen.
Additional Document Info
Colonie epithelial homeostasis is regulated by a balance between proliferation and apoplosis, which may change during the neoplastic process. In order to investigate this relationship as a function of fiber and carcinogen, we conducted a 2 x 2 factorial design study Groups of 10 male Sprague-Dawley rats were fed diets containing either cellulose (poorly fermented fiber) or pectin (highly fermented fiber) and injected with a colon-specific carcinogen (azoxymethane; AOM) or saline. Forty rats were killed 6 weeks after the second injection. In vivo cell proliferation was measured immunohistochemicalry using incorporation of bromodeoxyuridine into DNA. Apoptosis was measured by immunoperoxidase detection of digoxigenin-labeled genomic DNA. Results: In the proximal colon, pectin + AOM resulted in a labeling index that was numerically higher than cellulose + AOM (9.29 1.11 vs 9.16 0.59) and an apoplolic index that was numerically lower than cellulose (0.87 0.22 vs 1.19 0.26). The ratio of proliferation to apoptosis was 10.68 for pectin + AOM vs 7.70 for cellulose +AOM which may explain the greater number of cells per crypt column with pectin supplementation (26.78 vs 23.68; P- 0.03). In the distal colon, pectin + AOM also stimulated cell proliferation compared to cellulose + AOM (10.40 0.96 vs 9.57 1.45) and decreased apoptosis (1.44 0.30 vs 1.56 0.24) with a ratio of 7.22 for pectin + AOM vs 6.13 for cellulose + AOM. Interestingly, in the distal colon, rather than increasing the number of cells/crypt, the number of crypts/cm of intestine significantly increased with pectin + AOM (P=0.003). These data show that small changes in proliferation and apoptosis when taken together can result in highly significant effects on crypt size and number.