SUPPRESSION OF INTESTINAL POLYP DEVELOPMENT BY LOW-FAT AND HIGH-FIBERDIET IN APC(DELTA-716) KNOCKOUT MICE

Most epidemiological and animal studies show a positive correlation of the dietary intake of fat with the incidence of colon cancer, whereas an inverse correlation of the dietary intake of fiber, In rats fed a diet low in fat and high in wheat bran fiber and calcium, a significan t decrease was reported in the number of azoxymethane-induced aberrant crypt foci compared with those fed a high-fat, low-fiber and low-calc ium diet. Mutations in the human APC gene play a key role, not only in familial adenomatous polyposis, but also in many sporadic cancers of the entire digestive tract, We previously constructed a mouse strain A pc(Delta 716), carrying a truncation mutation at codon 716 of the Apc gene, the homolog of human APC (10). The heterozygous mice developed n umerous intestinal polyps, and all microadenomas dissected from the ea rliest polyps had already lost the wild-type allele, indicating the lo ss of heterozygosity, Using these Apc(Delta 716) knockout mice, we hav e investigated the effect of a low-fat and high-fiber diet (LRD for 'l ow-risk' diet) on intestinal polyposis, and compared it with that of a high-fat and low-fiber diet (HRD for 'high-risk' diet), The mice were fed either diet for 7 weeks, and the number and size of intestinal po lyps were scored, The LRD-fed mice had fewer polyps than the HRD-fed m ice, by 36% in the small intestine and by 64% in the colon, As for the polyp size distribution, there was no significant difference between the HRD-and LRD-fed mice, These results indicate that LRD can suppress intestinal polyposis compared with HRD which does not, and suggest th at its suppression is sat the initiation of polyp formation, This is l ikely to be due to a decreased frequency of loss of heterozygosity, ra ther than a retarded growth of the polyp adenomas.