DIETARY MODULATION OF DNA ADDUCT FORMATION OF THE FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN THE MALE FISCHER-344 RAT

In numerous in vivo systems it has been shown that diets high in menha den oil (a fish oil high in omega-3 fatty acids) can inhibit the carci nogenic process. in the present study, we have assessed the effects of a diet containing menhaden oil on 2-amino-3-methylimidazo[4,5-f]quino line (IQ)-DNA adduct formation in target tissues of the male Fischer 3 44 rat. Young adult male Fischer 341, rats were maintained on either a ) an AIN-76A diet containing 5% corn oil, b) an isocaloric AIN-76A die t modified to contain 2% corn oil and 19% menhaden oil (MO diet), or c ) a regular laboratory rodent diet (chow diet) for 6 weeks prior to re ceiving a single oral dose of 10 or 50 mg IQ/kg. Groups of four animal s were killed 1 or 6 days after 10 administration. Using P-32-postlabe ling assays, IQ-DNA adducts were isolated and quantitated in the liver small intestine, and large intestine. Adduct patterns were similar in all cases. Adduct levels, expressed as relative adduct labeling value s (RAL x 10(7)), were related to dose in all three tissues, with liver levels up to 10-fold higher than the large intestine and up to 20-fol d higher than the small intestine. On day one, liver adduct levels in animals on the AIN-76A diet were similar to those in animals on the ch ow diet, but those in animals on the MO diet were approximately 2-fold lower. On day six, these differences were much lower, probably as a r esult of the more efficient removal of liver adducts in animals on AIN -76A or chow diets. In the intestines, removal of adducts in animals o n either AIN-76A or MO diet was slower than that in the liver, while t hat in animals on the chow diet was similar to that in the liver. Whil e dietary MO is generally thought to inhibit experimental tumorigenesi s at the promotional stage, the present results show that MO diets may also inhibit the initiation process by inhibiting the initial rate of IQ-DNA adduct formation. It also appears, however, that MO diets may impair the process of adduct removal.