Effects of green tea catechins on the progression or late promotion stage of mammary gland carcinogenesis in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz(a)anthracene.

Effects of the green tea catechins (GTCs) on the late promotion or progression stage of mammary gland carcinogenesis were examined in female Sprague-Dawley (SD) rats pretreated with 7,12-dimethylbenz(a)anthracene (DMBA). A total of 84 7-week-old rats received a 50 mg/kg body weight intra-gastric dose of DMBA, and starting 13 weeks thereafter, when the tumor incidence had reached 50%, three groups of 28 animals each were placed on diet containing 0.5% Polyphenon E (58.4% content (-)-epigallocatechin gallate (EGCG)) (groups 1a and 1b), 0.5% EGCG-80 (81% content of EGCG) (groups 2a and 2b) or basal diet alone (groups 3a and 3b) for 23 weeks. The experiment was terminated at week 36. The growth (i.e. change in mean diameter) of mammary tumors present at week 13 (groups 1a, 2a and 3a) was not influenced by the treatment with EGCGs, with no significant intergroup differences in the lesion incidences, multiplicity or size being observed. Values for these parameters did show a tendency for decrease in group 2b (Polyphenon E) as compared to group 3b (control) during the study, but they were not significantly reduced at the sacrifice time point. These results indicate that GTCs are not effective at inhibiting progression of rat mammary carcinogenesis, but Polyphenon E may exert a weak inhibitory effect on the early promotion stage.

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- 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.