Carcinogenesis, Vol 18, 1863-1865, Copyright © 1997 by Oxford University Press
K Hioki, N Shivapurkar, H Oshima, O Alabaster, M Oshima and MM Taketo
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 significant decrease was
reported in the number of azoxymethane-induced aberrant crypt foci compared
with those fed a high-fat, low-fiber and low- calcium 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 Apc(delta716), carrying a
truncation mutation at codon 716 of the Apc gene, the homolog of human APC
(10). The heterozygous mice developed numerous intestinal polyps, and all
microadenomas dissected from the earliest polyps had already lost the
wild-type allele, indicating the loss of heterozygosity. Using these
Apc(delta716) knockout mice, we have investigated the effect of a low-fat
and high-fiber diet (LRD for 'low-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 polyps were scored. The LRD-fed mice had fewer polyps than
the HRD-fed mice, 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
that its suppression is at the initiation of polyp formation. This is
likely to be due to a decreased frequency of loss of heterozygosity, rather
than a retarded growth of the polyp adenomas.
ARTICLES
Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice
Central Institute for Experimental Animals, Kawasaki, Japan.
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