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Suppression of a Carcinogen (1,2-Dimethylhydrazine Dihydrochloride)-induced Increase in Mitotic Activity in the Colonic Crypts of Rats by Addition of Dietary Cellulose¹

Department of Cellular and Structural Biology [I. L. C., V. A. O., K. E. H., D. W. H.], The University of Texas Health Science Center, San Antonio, Texas 78284, and Department of Physiology [G. M. P.], Duke University Medical Center, Durham, North Carolina 27710

Serial injections of the colon carcinogen, 1,2-dimethylhydrazine (DMH), have been reported to increase the proliferative activity in the colonic crypts preceding development of tumors. Can addition of purified cellulose to a fiber-free AIN-76 rat diet be used to suppress this increase in proliferative activity? To answer this question rats were divided into two groups, and one group was given eight weekly injections of the DMH base at 9.5 mg/kg of body weight. Throughout this period and for 2 additional wk the rats were isocalorically fed a defined nutritionally complete diet both with and without different dietary levels of cellulose (0, 5, and 15%). The rats were given injections of colchicine 3 h prior to sacrifice to arrest and to collect dividing cells at metaphase. Analysis of variance was performed on various morphometric parameters obtained from histological sections of midaxial crypts from the descending colon. Our results confirm that DMH induced a significant increase in the mitotic activity as measured by the number of metaphase figures per crypt. The presence of dietary cellulose did cause a significant suppression of the DMH-induced increase in the crypt mitotic activity.

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 10/16/86. Revised 7/29/88. Revised 10/31/88. Accepted 10/31/88.

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