Chemopreventive effects of the
antioxidants 1-O-hexyl-2,3,5-
trimethylhydroquinone (HTHQ),
3-O-ethylascorbic acid (EAsA), 3-O-dodecylcarbomethylascorbic
acid (
DAsA),
green tea catechins (GTC) and
ellagic acid on 2-amino-1-methyl-6- phenylimidazo[4,5-
b]pyridine (
PhIP)-induced mammary
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 supplement for 52 weeks. The survival rates of
PhIP plus
antioxidant groups at the end of the experiment were higher than that of the
PhIP alone group. Sequential observation of palpable mammary
tumors demonstrated 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 final incidence of mammary
adenocarcinomas was significantly decreased in the
PhIP plus HTHQ group (4.8%, P < 0.01) as compared to the
PhIP alone 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 incidence 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.