Dietary ellagic acid reduces the esophageal microsomal metabolism of methylbenzylnitrosamine.
Dietary ellagic acid has been shown to reduce the incidence of methylbenzylnitrosamine-induced esophageal carcinoma in the rat. Methylbenzylnitrosamine (MBN) is a naturally occurring carcinogen which requires cytochrome P-450 dependent activation to be mutagenic. We examined whether the reduction in tumor incidence observed with dietary ellagic acid was associated with alterations in the cytochrome P-450 dependent microsomal metabolism of MBN. Dietary ellagic acid was shown to significantly reduce total esophageal and hepatic microsomal cytochrome P-450 (P less than 0.05) and significantly reduce the esophageal microsomal metabolism of MBN (P less than 0.05). The addition of ellagic acid in vitro also resulted in a significant inhibition (P less than 0.05) of the esophageal microsomal metabolism of MBN. In contrast, dietary ellagic acid and the addition of ellagic acid in vitro did not alter the hepatic microsomal metabolism of MBN. The reduced rate of MBN metabolism by the esophageal microsomes from the ellagic acid fed rats may contribute to the decreased incidence of esophageal carcinoma observed in these animals.
Barch
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Department of Medicine, University of Illinois, Chicago 60612.
Fox
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D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D004032:Diet; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D004610:Ellagic Acid / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000517:prevention & control; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001578:Benzopyrans; D004610:Ellagic Acid; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine