Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice

Most epidemiological and animal studies show a positive correlation of thedietary intake of fat with the incidence of colon cancer, whereas aninverse correlation of the dietary intake of fiber. In rats fed a diet lowin fat and high in wheat bran fiber and calcium, a significant decrease wasreported in the number of azoxymethane-induced aberrant crypt foci comparedwith those fed a high-fat, low-fiber and low- calcium diet. Mutations inthe human APC gene play a key role, not only in familial adenomatouspolyposis, but also in many sporadic cancers of the entire digestive tract.We previously constructed a mouse strain Apc(delta716), carrying atruncation mutation at codon 716 of the Apc gene, the homolog of human APC(10). The heterozygous mice developed numerous intestinal polyps, and allmicroadenomas dissected from the earliest polyps had already lost thewild-type allele, indicating the loss of heterozygosity. Using theseApc(delta716) knockout mice, we have investigated the effect of a low-fatand high-fiber diet (LRD for 'low-risk' diet) on intestinal polyposis, andcompared 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 sizeof intestinal polyps were scored. The LRD-fed mice had fewer polyps thanthe HRD-fed mice, by 36% in the small intestine and by 64% in the colon. Asfor the polyp size distribution, there was no significant differencebetween the HRD- and LRD-fed mice. These results indicate that LRD cansuppress intestinal polyposis compared with HRD which does not, and suggestthat its suppression is at the initiation of polyp formation. This islikely to be due to a decreased frequency of loss of heterozygosity, ratherthan a retarded growth of the polyp adenomas.