CHEMOPREVENTION OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]-PYRIDINE (PHIP)-INDUCED MAMMARY-GLAND CARCINOGENESIS BY ANTIOXIDANTS IN F344 FEMALE RATS

Chemopreventive effects of the antioxidants 1-O-hexyl-2,3,5-trimethyih ydroquinone (HTHQ), 3-O-ethylascorbic acid (EAsA), 3-O-dodecylcarbomet hylascorbic acid (DAsA), green tea catechins (GTC) and ellagic acid on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammar y carcinogenesis were examined in female F344 rats. Groups of 20-21 6- week-old rats were maintained on a powdered diet containing 0.02% PhIP alone, PhIP together with 0.5% HTHQ, 1% EAsA, 1% DAsA, 1% GTC or 0.1% ellagic acid, these antioxidants alone or basal diet alone without su pplement for 52 weeks. The survival rates of PhIP plus antioxidant gro ups at the end of the experiment were higher than that of the PhIP alo ne group. Sequential observation of palpable mammary tumors demonstrat ed only one tumor by week 52 in the PhIP plus HTHQ group, whereas 40% of the rats receiving PhIP alone had tumors by this time point. The fi nal incidence of mammary adenocarcinomas was significantly decreased i n the PhIP plus HTHQ group (4.8%, P < 0.01) as compared to the PhIP al one value (40%). Although statistically not significant, incidences of adenocarcinomas in the other antioxidant-treated groups (23.8-28.6%) were also lower than in the PhIP alone group. Furthermore, the inciden ce of large intestinal tumors in the PhIP plus HTHQ group (0%) showed a tendency to decrease relative to the PhIP alone group (16.7%). These results indicate that antioxidants, particularly HTHQ, exert a potent chemopreventive action against PhIP-induced carcinogenesis.