Carcinogenesis, Vol 18, 1905-1910, Copyright © 1997 by Oxford University Press
JE Paulsen, IK Elvsaas, IL Steffensen and J Alexander
We examined whether the n-3 polyunsaturated fatty acid ethyl ester enriched
fish oil K85 (54.4% of eicosapentaenoic acid and 30.3% of docosahexaenoic
acid as ethyl esters) could inhibit the intestinal tumorigenesis in Min
mice, a murine model of familial adenomatous polyposis (FAP). Min mice that
are heterozygous for a nonsense mutation in the Apc gene, develop
spontaneously multiple intestinal neoplasms, primarily in the small
intestine. K85 was dissolved in corn oil (vehicle) and mixed into the
AIN-76A diet. The total oil content (K85 + corn oil) was 12% in all diets.
The various experimental diets contained 0 (vehicle control), 0.4, 1.25 or
2.5% of K85. In the small intestine, the mean number of tumors/mouse was
105 +/- 18 (SEM) in control males and 70 +/- 11 in control females. Dietary
K85 treatment reduced the number of small intestinal tumors: in males, the
maximum reduction was 66% (P = 0.002) with 0.4% of K85; and in females, the
maximum reduction was 48% (P = 0.043) with 2.5% of K85, but the inhibition
was only slightly increased from 0.4% to 2.5% of K85. The mean tumor
diameter was 1.33 +/- 0.08 mm in control males and 1.06 +/- 0.08 in control
females, and the diameter ranged from <0.1 mm (monocryptal adenomas) to
4 mm. The small intestinal tumor diameter was reduced by K85 in a
dose-dependent manner: in males, with a maximum reduction of 26% (r =
-0.64, P = 0.004); and in females, with a maximum reduction of 38% (r =
-0.61, P < 0.004). In the large intestine, the mean number of
tumors/mouse was 1.0 +/- 0.5 in males and 0.8 +/- 0.2 in females. Although
K85 treatment tended to reduce the number and diameter of the large
intestinal tumors, these effects did not reach statistical significance.
Aberrant crypt foci not elevated from the flat mucosa (ACF(Min)) occurring
in the colon of Min mice were also scored. The mean number of
ACF(Min)/colon (3.8 +/- 0.9) and the crypt multiplicity (1.49 +/- 0.28) in
females were reduced by 73% (P = 0.03) and 60% (P = 0.048) with 2.5% of
K85, respectively, whereas no significant effect could be observed in the
males.
ARTICLES
A fish oil derived concentrate enriched in eicosapentaenoic and docosahexaenoic acid as ethyl ester suppresses the formation and growth of intestinal polyps in the Min mouse
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
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