| ABSTRACT: |
|
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. |