REDUCTION IN FORMATION OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP)-INDUCED ABERRANT CRYPT FOCI IN THE RAT COLON BY DOCOSAHEXAENOIC ACID (DHA)

Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of aberrant crypt foci induced by 1,2-dimethy lhydrazine and azoxymethane. In the present study we examined the effe cts of intragastric gavage administration of DHA on the yield of rat c olonic aberrant crypt foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), which induce s colon cancer in male F344 rats and is considered to be a possible hu man colon carcinogen, Male F344 rats were given a standard diet (AIN-7 6A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric i ntubation, on days 1-5 and 8-12) with or without intragastric applicat ion of 1 ml DHA 4 h prior to each carcinogen treatment, followed by fu rther DHA dosing, The numbers of PhIP-induced aberrant crypt foci per colon after 4 and 12 weeks DHA administration were significantly reduc ed to 47 and 38% respectively of the values obtained when PhIP alone w as used, The mean number of aberrant crypts per focus was also decreas ed by DHA treatment. At week 4 the PhIP-DNA adduct levels in the colon of rats from the PhIP+DHA group were approximately two thirds of the PhIP group value, The results thus suggest that DHA exerts a preventiv e effect on PhIP-induced colon carcinogenesis.