Polyposis coli: An experimental animal model

Abstract

Patients with familial polyposis, long standingulcerative colitis and ureterosigmoidostomies have an unstable colonic epithelium. There is a propensity for patients with the above conditions to develop colonic dysplasia and neoplasia. An experimental animal model using 1:2 dimethylhydrazine dihydrochloride (DMH) was used to induce dysplastic colonic lesions with a potential for neoplastic growth. This model was used to test the hypothesis that by altering the colonic environment one could change the natural history of the disease in this experimental model. In three separate experiments to test this hypothesis, the first set demonstrated the reliability of the model by inducing 8 to 10 tumors in the colon of each one of 65 experimental animals. These tumors are very similar in morphology to polyposis coli. The second set of experiments involved alteration of the colonic environment by having a group of rats on a high fiber diet. A total of 36 tumors were induced in the rats on a high fiber diet, whereas rats on a normal fiber diet had a total of 94 tumors induced. The high fiber diet protects a dysplastic colonic mucosa and alters the natural history of the disease in this experimental model (p value <0.01). The third set of experiments were designed in an attempt to identify the environmental factors responsible for the change in the course of the disease in rats on the high fiber diet. The fecal bile acid excretion, a known colon tumor promoter, was significantly reduced in rats on a high fiber diet (p value <0.01). The fecal residue which dilutes toxins and binds carcinogens onto dietary fiber as an ion exchange resin was found to be significantly increased in the rats on a high fiber diet (p value <0.01). The mean intestinal transit time which helps in the rapid elimination of any toxic waste products in the colonic environment was significantly diminished in rats on the high fiber diet (p value <0.05). The clinical relevance of this experimental model could be significant for pediatric patients who are predisposed to colonic neoplasia. The course of this disease could be changed if their colonic environment can be altered to protect them from factors operating on the unstable colonic epithelium. Patients with familial polyposis, long standingulcerative colitis and ureterosigmoidostomies have an unstable colonic epithelium. There is a propensity for patients with the above conditions to develop colonic dysplasia and neoplasia. An experimental animal model using 1:2 dimethylhydrazine dihydrochloride (DMH) was used to induce dysplastic colonic lesions with a potential for neoplastic growth. This model was used to test the hypothesis that by altering the colonic environment one could change the natural history of the disease in this experimental model. In three separate experiments to test this hypothesis, the first set demonstrated the reliability of the model by inducing 8 to 10 tumors in the colon of each one of 65 experimental animals. These tumors are very similar in morphology to polyposis coli. The second set of experiments involved alteration of the colonic environment by having a group of rats on a high fiber diet. A total of 36 tumors were induced in the rats on a high fiber diet, whereas rats on a normal fiber diet had a total of 94 tumors induced. The high fiber diet protects a dysplastic colonic mucosa and alters the natural history of the disease in this experimental model (p value <0.01). The third set of experiments were designed in an attempt to identify the environmental factors responsible for the change in the course of the disease in rats on the high fiber diet. The fecal bile acid excretion, a known colon tumor promoter, was significantly reduced in rats on a high fiber diet (p value <0.01). The fecal residue which dilutes toxins and binds carcinogens onto dietary fiber as an ion exchange resin was found to be significantly increased in the rats on a high fiber diet (p value <0.01). The mean intestinal transit time which helps in the rapid elimination of any toxic waste products in the colonic environment was significantly diminished in rats on the high fiber diet (p value <0.05). The clinical relevance of this experimental model could be significant for pediatric patients who are predisposed to colonic neoplasia. The course of this disease could be changed if their colonic environment can be altered to protect them from factors operating on the unstable colonic epithelium.