Measurement of the proliferative status of colonic epithelium as a risk marker for colon carcinogenesis: Effect of bile acid and dietary fiber

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Abstract
The proliferative status of mouse colonic epithelium, as affected by dietary fibers with or without cholic acid (CA), was studied by autoradiography and the metaphase arrest technique. In the first study, groups of mice were fed natural ingredient (laboratory chow) or semisynthetic diets containing 0% (control) or 0.2% (test) CA. After the mice were fed two weeks, the effect of CA was significantly more pronounced in the semisynthetic diet group than in the natural ingredient diet group with respect to labeled cells/crypt section (7.8 ± 0.8 vs. 2.9 ± 0.4) and mitotic figure (MF)/crypt section (3.0 ± 0.5 vs. 1.8 ± 0.2). In the second study, diets formulated to contain 5 or 10% cellulose (C), pectin (P), or wheat bran (WB) with or without CA (0.2%) were fed to animals for two weeks and colonic proliferative indices were measured. When compared with 5% C group, the 10% WB group exhibited lower labeling index (LI) values (4.2 ± 0.5 vs. 6.4 ± 1.0) and the 10% P group exhibited higher LI values (10.0 ± 1.1 vs. 6.4 ± 1.0). CA‐induced increases in the LI and MF values responded independently in some cases to dietary fiber. Among the CA‐treated groups, only the 10% P diet resulted in lower LI when compared with the 5% C group (p < 0.05) (7.4 ± 0.8 vs. 12.5 ± 2.8) but had no effect on MF/crypt section. However, the 5 or 10% WB diet resulted in lower MF values (1.7 ± 0.2 and 1.8 ± 0.6 vs. 2.6 ± 0.3). A long‐term feeding study comparing 10% P with 10% C diets also demonstrated that the LI was elevated in the 10% P group without any effect on the mitotic activity of the colonic epithelium. This paradoxiclal finding suggests that the value of the LI and/or mitotic index as a risk marker of colon carcinogenesis should be further investigated.