| ABSTRACT: |
|
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. |