If more were known about the role of diet in the cause of colon cancer, then specific dietary interventions could be recommended that would reduce the incidence of colon cancer. It has been observed that hyperplasia of colon epithelium precedes neoplasia and that the cell proliferation rate of colonic epithelium is correlated to carcinogen-induced neoplasia. Thus, nutritional modification of cell proliferation rate in the colon is hypothesized to modify the carcinogen-induced progression of normal eptihelium to the neoplastic state. To test this hypothesis we have designed experiments to give answers to the following specific questions regarding the progression of 1,2-dimethyl-hydrazine (DMH) treated colon eptihelium to the overt neoplastic state. 1. Is the reported prevention of DMH-induced hyperplasia in the colon, which was caused by administration of total parenteral (intravenous) nutrition ITPN) at isocaloric intake levels, permanent or reversible? If hyperplasia does not return after TPN treatment, is colon tumor incidence reduced by such TPN treatment? 2. Does a hypercaloric diet given to DMH-treated rats enhance colonic hyperplasia, and increase tumor incidence? 3. How does the manipulation of the non-nutritive fiber content in the diet, the caloric content of the diet, the chemical composition of the diet, one at a time while holding all other variables constant, affect interactions between such nutritional factors and carcinogen-included colonic neoplasia? Briefly, the experiments call for dietary modification either during, or after, or during and after an eight-week course of DMH treatment to rats. Groups of DMH and non-DMH treated rats will be sacrificed at times after the beginning of the carcinogen administration. To monitor the progression of colon carcinogenesis, the epithelium will be examined for: cell proliferation activity and crypt structure using histologic examination, intracellular content of sodium using X-ray microanalysis procedures, and also for the incidence and size of all visible tumors. The data will be subjected to appropriate statistical analysis. The findings should give insight into the interactions between nutritional factors and colonic carcinogenesis and should lead to nutritional concepts of prophylaxis against colon cancer. We will be on schedule with our original proposed experimental protocol by the end of this year and will follow the original proposed schedule of experimentation closely this next year.
| Cameron, I L; Ord, V A; Hunter, K E et al. (1990) Quantitative contribution of factors regulating rat colonic crypt epithelium: role of parenteral and enteral feeding, caloric intake, dietary cellulose level and the colon carcinogen DMH. Cell Tissue Kinet 23:227-35 |
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| Cameron, I L; Ord, V A; Hunter, K E et al. (1989) Suppression of a a carcinogen (1,2-dimethylhydrazine dihydrochloride)-induced increase in mitotic activity in the colonic crypts of rats by addition of dietary cellulose. Cancer Res 49:991-5 |
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