Enhancement of dimethylnitrosamine metabolism and activation to a mutagen following chronic ethanol consumption

Chronic ethanol ingestion in rats results in an increase in hepatic microsomal dimethylnitrosamine (DMN) demethylase activity and in an increase in hepatic microsomal activation of DMN to a mutagen. These effects of ethanol on DMN metabolism were detectable in vitro at DMN concentrations as low as 0.3 to 1 mM and as high as 100 mM. This ability of ethanol to increase the rate of DMN metabolism over such a broad range of DMN concentrations is in marked contrast to the effects of other microsomal enzyme inducers, such as phenobarbital and 3-methylcholanthrene, which increase the rate of DMN metabolism only at relatively high DMN concentrations and repress its metabolism at low DMN concentrations.