Modulation of urethane (ethyl carbamate) carcinogenicity by ethyl alcohol: A review

Urethane (ethyl carbamate) is a carcinogen that has been detected as a contaminant in certain foods and alcoholic beverages. The carcinogenicity of urethane appears to be mediated through a metabolic pathway involving sequential cytochrome P-450-catalyzed oxidation to vinyl carbamate and vinyl carbamate epoxide, the latter of which reacts with DNA to yield etheno-type DNA adducts. The interactions of ethanol on urethane metabolism and carcinogenicity are varied and complex. Urethane is oxidized by cytochrome P-450 IIE1, an isoform induced by ethanol, which suggests that chronic ethanol consumption could increase the oxidation of urethane to its epoxide derivative. On the other hand, ethanol coadministration is known to inhibit the elimination and hydrolysis of urethane. Ethanol has decreased the tumorigenicity of urethane in two bioassays, but did not have an effect in a third. While the results to elate suggest that ethanol will decrease the metabolic activation of urethane, with a resultant decrease in tumorigenicity, additional studies are clearly necessary to elucidate the mechanisms by which ethanol influences the carcinogenicity of urethane.