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Effect of Dietary Cellulose on Cell Proliferation and Progression of 1,2-Dimethylhydrazine-induced Colon Carcinogenesis in Rats¹

Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, Texas 78284

The effects of different levels of dietary cellulose on colonic crypt mitotic activity and colon carcinogenesis were studied in 190 male Sprague-Dawley rats. Rats were divided into groups and fed a basal fiber-free diet supplemented with either 0, 5, or 15% pure cellulose (w/w), for periods of 10 weeks (initiation stage) or 32 weeks (promotional stage). Half of the rats in each group were given weekly s.c. injections of 9.5 mg 1,2-dimethylhydrazine (the base) (DMH) for 8 weeks. Some of the rats were killed at 10 weeks while most were killed 22 weeks later. In some groups the dietary cellulose level was changed to a different level at 10 weeks. Food intake and body weight data showed that the rats within each experiment were isocalorically fed. There was a direct correlation between crypt height and the percentage of cellulose in the diet. Addition of 5 or 15% dietary cellulose during the initiation stage of carcinogenesis resulted in a significant increase in crypt height. Increasing dietary cellulose after the initiation stage (0 to 5% and 5 to 15%) or maintaining a high dietary cellulose level throughout both the initiation and promotional stages (15%) resulted in a significant increase in crypt height. A DMH-induced increase in mitotic activity that was observed during the initiation stage was no longer evident after the 22-week promotional stage. The significant DMH-induced increases in proliferative zone height and crypt height that were initially observed during the initiation stage were also observed after the 22-week promotional stage. These data indicate that the initial DMH-induced increases observed in proliferative zone height and crypt height are irrerversible.

Addition of 5 or 15% cellulose was found to suppress DMH-enhanced mitotic activity in the crypts of the descending colon during the initiation stage of carcinogenesis. This finding was correlated with a significantly lower incidence of adenocarcinomas in rats maintained on 5 or 15% cellulose throughout both the initiation and promotional stages.

¹ Supported by National Cancer Institute Grant CA36372 and American Cancer Society Grant BC-641.

² To whom requests for reprints should be addressed.

Received 12/12/88. Revised 5/25/89. Accepted 7/21/89.

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