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 concentrate K85 (51.0% of eicosapentaenoic acid, 35.3% of docosahexaenoic acid and 7.7% of other n-3 fatty acids, all as ethyl esters) could inhibit the initial formation of aberrant crypt foci and the later growth of pre-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) formation of aberrant crypt foci induced by azoxymethane (2 x 15 mg/kg body 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=0.009) 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-dependent reduction of the growth of pre-existing aberrant crypt Foci induced by dimethylhydrazine (3 x 20 mg/kg body weight/injection the first 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 crypt multiplication was further documented by the 63% reduction (P = 0.03) of the large aberrant crypt foci (foci with 9 or more aberrant crypts). The total number of aberrant crypt foci was not affected.