Inhibition of N-nitrosobenzylmethylamine metabolism and DNA binding in cultured rat esophagus by ellagic acid.
The effect of ellagic acid (EA), a naturally occurring plant phenol, on the metabolism, DNA binding and DNA adduct formation of N-nitrosobenzylmethylamine (NBMA) in cultured explants of rat esophagus was investigated. Explants were incubated in medium containing EA at non-toxic concentrations of 10, 50 and 100 microM for 16 h, followed by the addition of 1 microM [3H]NBMA and EA for 12 h. Explant DNA was isolated by phenol extraction and hydroxylapatite chromatography, and benzaldehyde formation was determined by HPLC analysis of the culture medium. EA produced a significant inhibition in the total covalent binding of NBMA metabolites to DNA and in the production of benzaldehyde in the medium. After acid hydrolysis of the isolated DNA, the NBMA--DNA adducts were separated by HPLC. EA caused a dose-dependent decrease in the formation of N7-methylguanine and O6-methylguanine adducts. These results suggest that EA inhibits both the metabolism of NBMA and the binding of NBMA metabolites to DNA in cultured rat esophagus.
Mandal
S
S
Department of Pathology, Medical College of Ohio, Toledo 43699.
Shivapurkar
N M
NM
Galati
A J
AJ
Stoner
G D
GD
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D004610:Ellagic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D051381:Rats
D001578:Benzopyrans; D004610:Ellagic Acid; D004247:DNA; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine