Ellagic acid,
quercetin and
robinetin were tested for their ability to antagonize the
tumor-initiating activity of
benzo[a]pyrene (B[a]P) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]
pyrene (B[a]P 7,8-diol-9,10-
epoxide-2), the ultimate carcinogenic metabolite of
benzo[a]-pyrene.
Ellagic acid,
robinetin or
quercetin (2500 nmol) had no
tumor-initiating activity on mouse skin, but the topical application of 2500 nmol of
ellagic acid 5 min before a
tumor-initiating dose of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 caused a 59-66% inhibition in the number of skin
tumors per mouse that were observed after 15-20 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Similar treatment with 2500 nmol of
robinetin or
quercetin caused a statistically insignificant 16-24% inhibition in the
tumor-initiating activity of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 applied 5 min later. Treatment of mice with 2500 nmol of
ellagic acid 5 min before the application of 50 nmol of B[a]P inhibited the mean number of skin
tumors per mouse by 28-33% after 15-20 weeks of promotion, but these decreases were not statistically significant.
Robinetin and
quercetin had little or no effect on the
tumor-initiating activity of B[a]P on mouse skin. Treatment of preweanling mice with 1/7, 2/7 and 4/7 of the total dose of
ellagic acid (300 nmol),
robinetin (1400 nmol),
myricetin (1400 nmol) or
quercetin (1400 nmol) i.p. on their first, eighth and fifteenth day of life, respectively, did not cause the formation of
tumors in animals that were killed 9-11 months later. Similar treatment of preweanling mice with the above doses of the phenolic compounds 10 min before the i.p. injection of a total dose of 30 nmol of B[a]P 7,8-diol-9,10-epoxide-2 during the animal's first 15 days of life caused a 44-75% inhibition in the number of diol-
epoxide-induced pulmonary
tumors per mouse. Similar treatment with these plant
phenols had little or no effect on B[a]P-induced pulmonary
tumors.