FORMATION AND PERSISTENCE OF DNA-ADDUCTS OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) IN CDF1 MICE FED A HIGH OMEGA-3-FATTY-ACID DIET

The potent bacterial mutagen 2-amino-3-methylimidazo[4,5-f]quinoline ( IQ) is carcinogenic in the CDF1 mouse, affecting the liver, lungs and forestomach. IQ forms DNA adducts in both target-and non-target organs of the CDF1 mouse. The chemopreventive effects of menhaden oil (MO), a fish oil high in omega-3 fatty acids, are well known. Because DNA ad duct formation is considered to be a critical event in the initiation of carcinogenesis, we have assessed the effects of dietary MO on IQ-DN A adduct formation. For the duration of the study, young adult, male C DF1 mice were maintained on either powdered chow diet, AIN-76A diet, o r AIN-76A diet modified to contain 19% MO (19% MO diet), After 2 weeks on these diets, all animals received 0.01% (w/w) IQ in the diet for t he next 3 weeks. Groups of 4 animals were killed 1, 2, 4, 6, 8 or 12 d ays thereafter for analysis of IQ-DNA adducts by P-32-postlabeling. IQ -DNA adduct patterns were qualitatively similar in the liver, lungs, s tomach, small intestine, cecum, colon, kidneys, heart and spleen. Addu ct levels in the liver, lungs, stomach and colon decreased significant ly during the 12-day study period, but only to a relatively small exte nt and only with certain of the diets. On day 1, the 19% MO diet signi ficantly decreased (35.8-90.0%) adduct levels in the stomach, cecum, c olon and kidneys, when compared to chow diet or AIN-76A diet. On day 1 2, adduct levels in the liver, stomach, heart and spleen were decrease d (36.5-64.7%) as a result of MO feeding. With the exception of the li ver, heart and spleen on day 12, there were no significant differences in organ adduct levels between the chow diet and the AIN-76A diet. It is concluded that feeding 0.01% (w/w) IQ in the diet for 3 weeks resu lts in a relatively slow rate of adduct removal and that this rate is largely independent of the type of diet. Dietary MO inhibits IQ-DNA ad duct formation only in certain target-and non-target organs of the CDF 1 mouse, a finding similar to our previous results in the F344 rat. MO may affect the initiation phase of IQ tumorigenesis by inhibiting IQ- DNA adduct formation in certain target organs. (C) 1997 Elsevier Scien ce B.V.