The objective of these studies is to study the effect of different forms of dietary calories and their restriction upon the incidence of chemically induced colon tumors, associated metabolite patterns, tissue enzymes and other tissue constituents. The effects of dietary calories from fat, protein and carbohydrate on cancer incidence will be studied in rats fed a 15% protein and 5% purified fat diet and treated intrarectally with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in 4 biweekly dosages at 56 to 70 days of age. Then they will be assigned to purified diets varying in protein, fat and carbohydrate. Comparisons of cancer incidence will be made with calorie intake reduced by classic methods of arbitrary feed restriction and by removal of 20 and 40% of calories supplied by fat and carbohydrate with proteins vitamins, minerals and fiber kept constant. Experiments will employ factorial designs and compare responses against those obtained with ad libitum feeding to determine the influence of calories from various sources. Tumors will be recorded by time of appearance, location and size, and histological characteristics. Metabolic balances will be determined in animals given MNNG and assigned to three levels of fat and three levels of protein to determine how the experimental treatments affect utilization of nitrogen, fat and energy and excretion of bile acids and lipids in feces. The urine content of N, energy, urea, uric acid, creatinine citrate and orotic acid will be determined. The serum will be assayed for fatty acids and cholesterol and the colon mucosa will be assayed for ornithine decarboxylase, S-adenosylmethionine decarboxylase activities and content of polyamines. Colon contents will be assayed for pH, ammonia and bacterial Beta-glucuronidase activity. The spectrum of fatty acids and bile acids excreted in feces will be determined.
