Dietary omega-3 fatty acids as potential inhibitors of carcinogenesis: Effect on DNA adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice and rats

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhI P) is carcinogenic in the CDF, mouse, causing lymphomas (spleen and lymph n odes) and in the F344 rat, causing mammary rumours in the female and colon rumours in the male. Dietary Fish oil, a rich sourer of omega-3 fatty acids , exhibits chemopreventive properties in several rodent tumour models. The potential chemopreventive properties of dietary omega-3 fatty acid ethyl ea ter concentrate (O3C) were tested by evaluating its effects on the formatio n and removal of PhIP DNA adducts. In the First experiment. a powdered AIN- 76A diet containing 4.0% (w/w) O3C inhibited PhIP-DNA adduct formation in v arious organs of the CDF, mouse, but not in those of the F344 rat. In a sub sequent, second experiment, groups of male CDF1 mice were maintained for 43 days on AIN-76A diets containing the following percentages (w/w) of corn o il ethyl esters and O3C: 7.0 and 0, 5.5 and 1.5, 4.0 and 3.0, and 1.0 and 6 .0, respectively. All animals received 0.04% (w/w) PhIP in the diet during weeks 3 and 4. Using P-32-postlabelling assays, PhIP-DNA adducts Here analy sed in various organs and white blood cells (WBC) on days 1, 8 and 15 after removal of PhIP From the dirt. In the liver, O3C-containing diets inhibite d adduct formation at all three time points (40.3-60.0%, 53.9-75.7% and 43. 3-64.3% on days 1, 8 and 15, respectively). In the spleen, inhibition a as evident only on days 8 (35.4-38.8%) and 15 (38.4-56.5%). O3C diets inhibite d adduct formation in the stomach, small intestine and caecum at all three time points (except in the stomach and caecum on day 15) amounting to 18.5- 31.5% decreases in the stomach, 40.0 60.3% decreases in the small intestine and 24.4-31.4% decreases in the caecum. The extant of inhibition was not r elated to O3C concentration In the colon and WBC, adduct levels were indepe ndent of the type of diet. In all organs, adduct levels decreased significa ntly over time, with day 15 levels bring 6.3-31.6% of those on day 1. Rate of adduct removal was independent of the type of diet. It is concluded that dietary O3C inhibits PhIP DNA adduct formation in a target organ (spleen) as well as in non-target organs (liver and gastrointestinal tract) of the C DF1 mouse, but that the rate of adduct removal is independent of the O3C co ntent of the diet. (C) 1999 Elsevier Science Ltd. All rights reserved.