Dietary ellagic acid inhibits the enzymatic activity of CYP1A1 without altering hepatic concentrations of CYP1A1 or CYP1A1 mRNA.
The anticarcinogen ellagic acid significantly reduces the incidence of polycyclic aromatic hydrocarbon induced carcinomas, in association with significant reductions in benzo[a]pyrene hydroxylase activity and CO reducible hepatic cytochrome P450. This suggested that ellagic acid reduced hepatic concentrations of CYP1A1, but these changes occurred without any alteration in CYP1A1 mRNA or in immunoreactive CYP1A1. Dietary ellagic acid results in muMolar concentrations of ellagic acid in hepatic tissue. Addition of similar concentrations of ellagic acid in vitro directly inhibited the measurement of benzo[a]pyrene hydroxylase activity and CO reducible cytochrome P450. Thus dietary ellagic acid does not alter the hepatic concentration of CYP1A1, but the dietary ellagic acid remaining in hepatic tissue appears to directly inhibit the measurement of benzo[a]pyrene hydroxylase activity and CO reducible cytochrome P450.
Department of Medicine, Lakeside Veterans Affairs Medical Center, Northwestern University Medical School, Chicago, Illinois.
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Barch
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Rundhaugen
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Thomas
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Kardos
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Pillay
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D004610:Ellagic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D004610:Ellagic Acid; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System