title: 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.
abstract: 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 adduct formation is considered to be a critical event in the initiation of carcinogenesis, we have assessed the effects of dietary MO on IQ-DNA adduct formation. For the duration of the study, young adult, male CDF1 mice were maintained on either powdered chow diet, AIN-76A diet, or 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 the next 3 weeks. Groups of 4 animals were killed 1, 2, 4, 6, 8 or 12 days thereafter for analysis of IQ-DNA adducts by 32P-postlabeling. IQ-DNA adduct patterns were qualitatively similar in the liver, lungs, stomach, small intestine, cecum, colon, kidneys, heart and spleen. Adduct levels in the liver, lungs, stomach and colon decreased significantly during the 12-day study period, but only to a relatively small extent and only with certain of the diets. On day 1, the 19% MO diet significantly decreased (35.8-90.0%) adduct levels in the stomach, cecum, colon and kidneys, when compared to chow diet or AIN-76A diet. On day 12, adduct levels in the liver, stomach, heart and spleen were decreased (36.5-64.7%) as a result of MO feeding. With the exception of the liver, 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 results 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 adduct formation only in certain target- and non-target organs of the CDF1 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.
authors.affiliation: Department of Pathology, Medical College of Ohio, Toledo 43614, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Schut
authors.forename: C L
authors.initials: CL
authors.lastname: Wang
authors.forename: L M
authors.initials: LM
authors.lastname: Twining
authors.forename: K M
authors.initials: KM
authors.lastname: Earle
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D002855:Chromatography, Thin Layer; D003106:Colon / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage*; D005753:Gastric Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D011804:Quinolines / Q000378:metabolism* / Q000633:toxicity
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D009153:Mutagens; D011804:Quinolines; C033266:Menhaden oil; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D000255:Adenosine Triphosphate; D004247:DNA