Vinyl carbamate epoxide, a major strong electrophilic, mutagenic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate (urethane)

Carcinogenesis. 1993 Mar;14(3):441-50. doi: 10.1093/carcin/14.3.441.


Vinyl carbamate epoxide (VCO) was found to possess strong electrophilic, mutagenic and carcinogenic activities. It reacted with water at 37 degrees C and pH 7.4 (phosphate buffer) to form glycolaldehyde and several related reducing compounds; none of these products were mutagenic for Salmonella typhimurium TA1535. Under these conditions VCO had a half-life (determined chemically and mutagenically) of approximately 10.5 min. This half-life was progressively lowered by increasing concentrations of chloride ion (liver, serum and isotonic levels). This ion reacted with VCO to form chloroacetaldehyde. VCO also reacted with other nucleophiles such as glutathione, DNA and its constituent guanine and adenine bases. The purine adducts formed by VCO in DNA in vitro and in vivo were released by weak acid treatment and consisted of 7-(2'-oxoethyl)guanine and N2,3-ethenoguanine as major products with 1,N6-ethenoadenine as a minor product. VCO was a strong direct mutagen in Salmonella typhimurium TA1535 and TA100 but was only weakly active in the TA98 mutant. VCO was a stronger initiator of carcinogenesis in the skin of CD-1 mice and in the liver of infant male B6C3F1 mice than its metabolic precursors vinyl carbamate (VC) and ethyl carbamate (EC). Unlike VC and EC, VCO was a strong complete carcinogen in the skin of CD-1 mice and induced papillomas and carcinomas following repetitive administration of sub-ulcerogenic doses. VCO also exhibited some carcinogenic activity in the lungs of mice and in the s.c. and mammary tissue of female Sprague-Dawley rats. These data and those from other recent studies support the conclusion that VCO is a major strong electrophilic, mutagenic and carcinogenic metabolite of EC and VC in the mouse.

Publication types

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

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • DNA / metabolism
  • Female
  • Glutathione / pharmacology
  • Glutathione Transferase / pharmacology
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mutagens / toxicity*
  • Neoplasms, Experimental / chemically induced
  • Rats
  • Rats, Sprague-Dawley
  • Urethane / analogs & derivatives*
  • Urethane / metabolism*
  • Urethane / toxicity


  • Carcinogens
  • Mutagens
  • Urethane
  • vinyl carbamate
  • vinyl carbamate epoxide
  • DNA
  • Glutathione Transferase
  • Glutathione