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-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.
Takahashi
M
M
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Totsuka
Y
Y
Masuda
M
M
Fukuda
K
K
Oguri
A
A
Yazawa
K
K
Sugimura
T
T
Wakabayashi
K
K
D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018736:DNA Adducts / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D007093:Imidazoles / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; D004281:Docosahexaenoic Acids; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine