Effect of ellagic acid and 3-O-decylellagic acid on the formation of benzo[a]pyrene-derived DNA adducts in vivo and on the tumorigenicity of 3-methylcholanthrene in mice.

The effect of ellagic acid and its more lipophilic derivative, 3-O-decylellagic acid, on the amount of DNA-bound adducts in the epidermis or lung of CD-1 mice treated with [3H]benzo-[a]pyrene ([3H]B[a]P) was evaluated using several different treatment protocols. The i.v. administration of 50 mumol/kg of ellagic acid or 3-O-decylellagic acid either together with or 5 min before a 0.2 mumol/kg i.v. dose of [3H]B[a]P did not inhibit the formation of pulmonary DNA-bound adducts. Feeding mice a diet that contained 1% ellagic acid for 10 days or the i.p. administration of 120 mumol/kg of ellagic acid 30 min before the i.v. administration of 0.2 mumol/kg of [3H]B[a]P did not inhibit the formation of DNA-bound adducts in the lung. The application of 2,500 nmol of ellagic acid or 3-O-decylellagic acid to mouse skin 5 min before the application of 2, 10 or 50 nmol of [3H]B[a]P had little or no effect on the covalent binding of [3H]B[a]P metabolites to epidermal DNA. Feeding mice a diet containing 1% ellagic acid for 10 days did not inhibit the formation of epidermal DNA-bound adducts after a topical dose of 2 nmol of [3H]B[a]P. Similarly, the topical application of 2,500 nmol of ellagic acid at 2 h, 1 h and 5 min before and at 10 min after the application of 2 nmol of [3H]B[a]P did not inhibit the formation of DNA-bound adducts, but the same dosing regimen of 3-O-decylellagic acid (total dose of 10,000 nmol) resulted in a modest inhibition in the formation of DNA-bound adducts. The topical application of 1,500 nmol of ellagic acid 1 h before the application of 1,500 nmol of 3-methylcholanthrene (3-MC) to CD-1 or BALB/c mice twice weekly did not inhibit the development of skin tumors. Our results indicate that ellagic acid and 3-O-decylellagic acid are not effective in inhibiting [3H]B[a]P DNA adduct formation in mouse skin and lung and that ellagic acid does not inhibit 3-MC-induced skin tumorigenesis in BALB/c or CD-1 mice.