Effects of dietary menhaden oil on DNA adducts of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Fischer-344 rats.
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a food mutagen which has been found to be carcinogenic in the Fischer-344 rat. We have assessed the effects of a diet containing menhaden oil on IQ-DNA adduct formation in several organs of the male Fischer-344 rat. Young adult, male Fischer-344 rats were maintained on either a) an AIN-76A diet, containing 5% corn oil, or b) an isocaloric AIN-76A diet modified to contain 2% corn oil and 19% menhaden oil (MO diet), or c) a regular laboratory rodent diet (chow diet) for six weeks prior to receiving a single p.o. dose of 10 or 50 mg IQ/kg. Groups of four animals were killed one or six days after IQ administration. Using 32P-postlabeling assays, IQ-DNA adducts were isolated and quantitated in the liver, lungs, stomach, small intestine, large intestine, kidney, heart, spleen and white blood cells. Adduct patterns were similar in all cases and adduct levels, expressed as relative adduct labeling values (RAL x 10(7), were related to dose in all organs. Adduct formation was dependent on the diet and in almost all organs adduct levels in animals on the AIN-76A diet were similar to those on the chow diet. The 19% MO diet inhibited adduct formation in several organs, but not in others. On day 6 there was evidence of impairment of adduct removal in a number of organs of animals on the 19% MO diet and in several organs of animals on the AIN-76A diet, but not in animals on the chow diet. While dietary MO is generally thought to inhibit experimental tumorigenesis 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.
Schut
H A
HA
Department of Pathology, Medical College of Ohio Toledo 43699.
D000818:Animals; D004247:DNA / Q000378:metabolism*; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D005395:Fish Oils; D011804:Quinolines; C033266:Menhaden oil; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA