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Effects of Ammonium Acetate and Sodium Cholate on N-Methyl-N'-nitro-N-nitrosoguanidine-induced Colon Carcinogenesis of Rats¹

The University of Illinois College of Medicine, Urbana, Illinois 61801 [S. K. C., H. J. M., W. J. V.], and the University of Chicago Hospitals and Clinics, Chicago, Illinois 60637 [D. G. B., L. M. O.]

This study was conducted to determine the effects of ammonium acetate alone or in combination with sodium cholate upon N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced colon carcinogenesis in rats. Ammonia, acetate, and deconjugated bile acids are produced by microbial enzymes in the gastrointestinal lumen. One hundred twenty male Sprague-Dawley rats, weighing 196 ± 2 g at 8 wk of age, were given four intrarectal doses of MNNG (2 mg/dose) over 2 wk. They were then randomly assigned among four treatment groups, each containing 30 rats. The groups were arranged in a 2 x 2 factorial design and given intrarectal infusions of the agents under study in 0.3 ml of double-distilled water 3 times weekly for 52 wk beginning 4 wk after the initial MNNG treatment. The experimental treatments were: double-distilled water as control; ammonium acetate (24.8 mg of ammonia); sodium cholate (2 mg of cholic acid); and a combination of ammonium acetate and sodium cholate. Ammonium acetate treatment increased the number of rats with fecal blood 4-fold after 56 wk, and this was associated with a higher incidence of adenocarcinomas with a polypoid morphology. The incidence and total number of carcinomas in situ (high grade dysplasia) increased with ammonium acetate treatment. Ammonium acetate increased the total number of adenocarcinomas. Sodium cholate had no significant main effects on the incidence or morphology of colon lesions. The data support the conclusion that ammonium acetate treatment acted as a promoting agent in MNNG-induced colon carcinogenesis.

¹ Supported by Grant CA33796, NIH, Department of Health and Human Services. The care and use of laboratory animals were in accordance with the "Public Health Service Policy on Human Care and Use of Laboratory Animals," revised September 1986.

² Present address: USDA-Human Nutrition Research Center on Aging, Tufts University, 711 Washington St., Boston, MA 02111.

³ To whom requests for reprints should be addressed, at 190 Medical Sciences Building, 506 S. Mathews Ave., University of Illinois, Urbana, IL 61801.

Received 7/27/87. Revised 11/17/87. Revised 2/23/88. Accepted 3/ 3/88.

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