Mechanism of inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA binding by ellagic acid.
Ellagic acid (EA) is a dilactone derivative of shikimic acid, which is found in a variety of soft fruits and vegetables. EA inhibits mutagenesis and carcinogenesis induced by benzo[a]pyrene and its bay-region dihydrodiol epoxide derivative by preventing their covalent binding to DNA. EA at concentrations of 100, 250, 500 and 1000 nmol/plate inhibited the mutagenicity of N-methyl-N-nitrosourea (MNU) (400 nmol/plate) in Salmonella typhimurium TA100 by 3, 13, 45 and 60%, respectively. A study of inhibition of 3H-MNU-mediated DNA methylation by EA showed that it inhibited only the formation of O6-methylguanine, while attack at the N7 and N3 positions of guanine and adenine, respectively, was not altered. This inhibition was observed only in double-stranded DNA. Ultraviolet and equilibrium dialysis studies show that EA has a definite affinity for DNA, but that an intercalating process is not involved.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004610:Ellagic Acid / Q000494:pharmacology*; D005638:Fruit; D008745:Methylation; D008770:Methylnitrosourea / Q000037:antagonists & inhibitors*; D009154:Mutation / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D051381:Rats; D014675:Vegetables
D001578:Benzopyrans; D004610:Ellagic Acid; D012313:RNA; D008770:Methylnitrosourea; D004247:DNA