Inhibition of N-nitrosobenzylmethylamine metabolism and DNA binding in cultured rat esophagus by ellagic acid

Carcinogenesis. 1988 Jul;9(7):1313-6. doi: 10.1093/carcin/9.7.1313.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzopyrans / pharmacology*
  • Chromatography, High Pressure Liquid
  • DNA / metabolism
  • DNA Damage*
  • Dimethylnitrosamine / analogs & derivatives*
  • Dimethylnitrosamine / antagonists & inhibitors
  • Dimethylnitrosamine / metabolism
  • Ellagic Acid / pharmacology*
  • In Vitro Techniques
  • Rats

Substances

  • Benzopyrans
  • Ellagic Acid
  • DNA
  • nitrosobenzylmethylamine
  • Dimethylnitrosamine