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

We examined whether the n-3 polyunsaturated fatty acid ethyl ester enr iched fish oil K85 (54.4% of eicosapentaenoic acid and 30.3% of docosa hexaenoic acid as ethyl esters) could inhibit the intestinal tumorigen esis in Min mice, a murine model of familial adenomatous polyposis (FA P), Min mice that are heterozygous for a nonsense mutation in the Apc gene, develop spontaneously multiple intestinal neoplasms, primarily i n the small intestine, K85 was dissolved in corn oil (vehicle) and mix ed into the AIN-76A diet, The total oil content (K85 + corn oil) was 1 2% in all diets, The various experimental diets contained 0 (vehicle c ontrol), 0.4, 1.25 or 2.5% of K85, In the small intestine, the mean nu mber of tumors/mouse was 105 +/- 18 (SEM) in control males and 70 +/- 11 in control females, Dietary K85 treatment reduced the number of sma ll intestinal tumors: in males, the maximum reduction was 66% (P = 0.0 02) 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 incre ased 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 d iameter ranged from <0.1 mm (monocryptal adenomas) to 4 mm, The small intestinal tumor diameter was reduced by K85 in a dose-dependent manne r: in males, with a maximum reduction of 26% (r = -0.64, P = 0.004); a nd 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, thes e 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 reduc ed by 73% (P = 0.03) and 60% (P = 0.048) with 2.5% of K85, respectivel y, whereas no significant effect could be observed in the males.