title: 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.
abstract: 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.
authors.affiliation: Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
authors.forename: J E
authors.initials: JE
authors.lastname: Paulsen
authors.forename: T
authors.initials: T
authors.lastname: Stamm
authors.forename: J
authors.initials: J
authors.lastname: Alexander
mesh_terms: D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004127:Dimethylhydrazines; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens; D004127:Dimethylhydrazines; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D001397:Azoxymethane