A FISH OIL-DERIVED CONCENTRATE ENRICHED IN EICOSAPENTAENOIC AND DOCOSAHEXAENOIC ACID AS ETHYL-ESTERS INHIBITS THE FORMATION AND GROWTH OF ABERRANT CRYPT FOCI IN RAT COLON

It was examined whether the fish oil derived n-3 fatty acid concentrat e K85 (51.0% of eicosapentaenoic acid, 35.3% of docosahexaenoic acid a nd 7.7% of other n-3 fatty acids, all as ethyl esters) could inhibit t he initial formation of aberrant crypt foci and the later growth of pr e-existing aberrant crypt foci in the colon of male F344 rats treated with the carcinogens dimethylhydrazine or azoxymethane, the proximate metabolite of dimethylhydrazine. Given intragastrically 5 times a week , K85 caused a dose-dependent reduction of the initial (week 0-6) form ation of aberrant crypt foci induced by azoxymethane (2 x 15 mg/kg bod y weight/injection the first two weeks). The number of aberrant crypt foci was reduced by 36% (P<0.001) with 3.0 g K85/kg body weight/dose, the largest dose tested. The reduction was most pronounced (46%, P=0.0 09) among the fastest growing aberrant crypt foci (foci with 3 or more aberrant crypts). When given in a later phase of the carcinogenesis ( week 17-23) a similar intragastric treatment with K85 caused a dose-de pendent reduction of the growth of pre-existing aberrant crypt Foci in duced by dimethylhydrazine (3 x 20 mg/kg body weight/injection the fir st week). The crypt multiplicity (aberrant crypt/focus) was reduced by 22% (P = 0.016) with 2.24 g K85/kg body weight/dose, the largest dose tested. This was sufficient to completely block the growth of the pre -existing aberrant crypt foci in the treatment period. The arrest of c rypt multiplication was further documented by the 63% reduction (P = 0 .03) of the large aberrant crypt foci (foci with 9 or more aberrant cr ypts). The total number of aberrant crypt foci was not affected.