| AUTHOR: |
|
Chang RL, Huang MT, Wood AW, Wong CQ, Newmark HL, Yagi H, Sayer JM,
Jerina DM, Conney AH |
| ABSTRACT: |
|
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. |