Ellagic acid binding to DNA as a possible mechanism for its antimutagenic and anticarcinogenic action

Ellagic acid (EA), a plant phenol, is reported to possess antimutagenic and anticarcinogenic activity. In the present study, explants of esophagus, trachea, colon, forestomach and bladder from young male Sprague-Dawley rats were incubated in medium containing [3H]EA (4.5 mu Ci/ml) for 24 h at 37 degrees C. DNA from these explants was extracted, purified and quantitated to determine [3H]EA binding to the DNA. Significant covalent binding of [3H]EA to DNA occurred in all the explants. Calf thymus DNA incubated in 0.05 M sodium phosphate buffer containing [3H]EA covalently bound [3H]EA in a concentration dependent manner. Furthermore covalent binding of [3H]EA to calf thymus DNA was inhibited by the addition of unlabeled EA that was concentration dependent over a range of 50-150 microM and by the addition of unlabeled adenosine, cytidine, guanosine or thymidine at a concentration of 1.0 mM. These results suggest that one of the mechanisms by which EA inhibits mutagenesis and carcinogenesis is by forming adducts with DNA, thus masking binding sites to be occupied by the mutagen or carcinogen.