DIETARY ELLAGIC ACID INHIBITS THE ENZYMATIC-ACTIVITY OF CYP1A1 WITHOUT ALTERING HEPATIC CONCENTRATIONS OF CYP1A1 OR CYP1A1 MESSENGER-RNA

The anticarcinogen ellagic acid significantly reduces the incidence of polycyclic aromatic hydrocarbon induced carcinomas, in association wi th significant reductions in benzo[a]pyrene hydroxylase activity and C O reducible hepatic cytochrome P450. This suggested that ellagic acid reduced hepatic concentrations of CYP1A1, but these changes occurred w ithout any alteration in CYP1A1 mRNA or in immunoreactive CYP1A1. Diet ary ellagic acid results in mu Molar concentrations of ellagic acid in hepatic tissue. Addition of similar concentrations of ellagic acid in vitro directly inhibited the measurement of benzo[a]pyrene hydroxylas e activity and CO reducible cytochrome P450. Thus dietary ellagic acid does not alter the hepatic concentration of CYP1A1, but the dietary e llagic acid remaining in hepatic tissue appears to directly inhibit th e measurement of benzo[a]pyrene hydroxylase activity and CO reducible cytochrome P450. (C) 1994 Academic Press, Inc.