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Proliferative Activity in the Colon of the Mouse and Its Modulation by Dietary Starch, Fat, and Cellulose¹

Department of Pharmacology, University of Florence, Italy [G. C., F. B., P. D.]; and the Department of Environmental Science and Physiology, Harvard School of Public Health, Cambridge, Massachusetts [D. K.]

The effect of dietary starch, fat, and cellulose on colonic proliferation was studied in female C57B1/6J mice after 4 weeks of feeding with diets containing various levels of starch (3, 36, and 57–65%), various levels of fat (corn oil, 5 and 29%) and various levels of cellulose (2 and 10%). Cell proliferation was measured by colchicine arrest and [³H]thymidine incorporation. The following parameters were analyzed: mitotic index, labeling index, and position of labelled cells along the crypt.

Increasing starch content from 3 to 36% decreased cell proliferation both in low (5%) and high (29%) fat diets. By estimating simultaneously the effects of starch and fat with a single multiple regression model, we observed a decrease of mitotic index from 3.04 ± 0.34 to 2.04 ± 0.43 (means ± SE) (P < 0.05) when starch was increased from 3 to 36% regardless of the level of fat. Other proliferation parameters showed a similar pattern. Changes in dietary fat alone did not affect significantly cell proliferation. We also investigated the effect of starch at high levels (57–65%) and its interactions with cellulose. High starch (57–65%) increased the labeling index from 7.70 ± 0.58 to 9.65 ± 0.88 (P < 0.05), when also considering the effect of cellulose in the multiple regression model. Cellulose by itself did not change the labeling index. Varying starch from 36 to 57–65% increased the number of cells/crypt column from 22.20 ± 0.82 to 25.87 ± 1.21 (P<0.05) and varying cellulose from 2 to 10% increased the number of cells/crypt column from 22.20 ± 0.82 to 27.25 ± 0.97 (P < 0.01).

The results indicate that either high or low fat diets, containing 36% starch, have the minimum proliferative effects in the mouse colon. However, diets containing high levels of both starch (57%) and cellulose (10%) may induce an increase in proliferation. These data suggest a potential beneficial effect of starch on colon proliferation.

¹ This work was supported by C.N.R., M.P.I., and by the Nutrition Foundation of Italy. D. Kriebel was supported in part by the U. S. National Institute of Environmental Sciences, Grant R01-ES04202, and by a fellowship from la Commissione per gli Scambi Culturali fra l'Italia e gli Stati Uniti.

Received 7/18/88. Revised 11/18/88. Accepted 1/ 5/89.