Enhancement of dimethylnitrosamine metabolism and activation to a mutagen following chronic ethanol consumption
Garro, A.J.; Seitz, H.K.; Lieber, C.S.
Cancer Research 41(1): 120-124
1981
ISSN/ISBN: 0008-5472 PMID: 7192597 Document Number: 171775
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.