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)

Carcinogenesis. 1997 Oct;18(10):1937-41. doi: 10.1093/carcin/18.10.1937.


Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of aberrant crypt foci induced by 1,2-dimethylhydrazine and azoxymethane. In the present study we examined the effects of intragastric gavage administration of DHA on the yield of rat colonic aberrant crypt foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which induces colon cancer in male F344 rats and is considered to be a possible human colon carcinogen. Male F344 rats were given a standard diet (AIN-76A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric intubation, on days 1-5 and 8-12) with or without intragastric application of 1 ml DHA 4 h prior to each carcinogen treatment, followed by further DHA dosing. The numbers of PhIP-induced aberrant crypt foci per colon after 4 and 12 weeks DHA administration were significantly reduced to 47 and 38% respectively of the values obtained when PhIP alone was used. The mean number of aberrant crypts per focus was also decreased 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 preventive effect on PhIP-induced colon carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / metabolism
  • Carcinogens / toxicity*
  • Colon / drug effects*
  • Colon / metabolism
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • DNA Adducts / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Imidazoles / metabolism
  • Imidazoles / toxicity*
  • Male
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / prevention & control
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / prevention & control*
  • Rats
  • Rats, Inbred F344


  • Carcinogens
  • DNA Adducts
  • Imidazoles
  • Docosahexaenoic Acids
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine