This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dahl, G. A. Articles by Miller, J. A. Search for Related Content PubMed PubMed Citation Articles by Dahl, G. A. Articles by Miller, J. A.

Comparative Carcinogenicities and Mutagenicities of Vinyl Carbamate, Ethyl Carbamate, and Ethyl N-Hydroxycarbamate¹

McArdle Laboratory for Cancer Research, University of Wisconsin Center for Health Sciences, Madison, Wisconsin 53706

When administered during the first 5 weeks after birth, vinyl and ethyl carbamates each induced ear duct and hepatic carcinomas and neurofibrosarcomas of the ear lobe in Fischer rats. Vinyl carbamate was more active than ethyl carbamate for the induction of the latter two types of tumors. Similarly, vinyl carbamate administered in the first 3.5 weeks after birth induced more liver tumors, thymomas, lung adenomas, and Harderian gland tumors in C57BL/6J x C3H/HeJ F₁ mice than did ethyl carbamate. These data extend our earlier data on the much greater potency of vinyl carbamate than of ethyl carbamate for the induction of lung adenomas in A/J and CD-1 mice and for the initiation of skin tumors in CD-1 mice. CD₃CD₂OCONH₂ did not differ significantly from CH₃CH₂OCONH₂ for the induction of lung tumors in A/J mice; tert-butyl carbamate had no significant activity in the latter mouse strain.

High doses of the mixed-function oxidase inhibitor 2-(2,4-dichloro-6-phenyl)phenoxyethylamine inhibited the induction of lung adenomas in A/J mice by ethyl N-hydroxycarbamate; lung tumor induction by ethyl or vinyl carbamate was not inhibited. A lower dose of the above inhibitor or of 2-diethylaminoethyl-2,2-diphenylvalerate did not significantly inhibit lung adenoma induction by any of these carbamates. In confirmation of previous reports by other investigators, administration of caffeine concurrently with ethyl carbamate inhibited the formation of lung adenomas in A/J mice; no consistent inhibition was obtained under the same conditions when vinyl carbamate or ethyl N-hydroxycarbamate was the carcinogen.

Since reduced nicotinamide adenine dinucleotide phosphate-fortified duck liver microsome-cytosol preparations can dehydrogenate aflatoxin B₂ (2,3-CH₂CH₂) to aflatoxin B₁ (2,3CH=CH), the ability of this system to convert ethyl carbamate to vinyl carbamate was examined. Vinyl carbamate was not detected as a metabolite. Furthermore, ethyl carbamate was not mutagenic for Salmonella typhimurium TA 100 in the presence of a rat and duck liver system that metabolized both vinyl carbamate and aflatoxin B₂ to mutagens. Ethyl N-hydroxycarbamate showed very weak direct mutagenic activity (2 to 3 revertants/µmol) for S. typhimurium strains TA 98, TA 1535, and TA 100; both duck and rat liver preparations fortified with reduced nicotinamide adenine dinucleotide phosphate and reduced nicotinamide adenine dinucleotide reduced the mutagenic activity.

An improved synthesis of vinyl carbamate, similar to that developed independently by Olofson et al. for some N-substituted enol carbamates, is presented.

¹ This work was supported by Grants CA-07175, CA-22484, and CA-09135 from the National Cancer Institute, USPHS.

² Present address: Centre National de Recherches Agronomiques, Route de Saint-Cyr, 78000 Versailles, France.

³ To whom requests for reprints should be addressed.

Received 10/22/79. Accepted 1/ 7/80.

This article has been cited by other articles:

				L. G. Hernandez and P.-G. Forkert Inhibition of vinyl carbamate-induced mutagenicity and clastogenicity by the garlic constituent diallyl sulfone in F1 (Big Blue(R) x A/J) transgenic mice Carcinogenesis, August 1, 2007; 28(8): 1824 - 1830. [Abstract] [Full Text] [PDF]

				P.-G. Forkert, M. Kaufmann, G. Black, R. Bowers, H. Chen, K. Collins, A. Sharma, and G. Jones Oxidation of Vinyl Carbamate and Formation of 1,N6-Ethenodeoxyadenosine in Murine Lung Drug Metab. Dispos., May 1, 2007; 35(5): 713 - 720. [Abstract] [Full Text] [PDF]

				B. I. Ghanayem Inhibition of Urethane-Induced Carcinogenicity in Cyp2e1-/- in Comparison to Cyp2e1+/+ Mice Toxicol. Sci., February 1, 2007; 95(2): 331 - 339. [Abstract] [Full Text] [PDF]

				U. Hoffler and B. I. Ghanayem INCREASED BIOACCUMULATION OF URETHANE IN CYP2E1-/- VERSUS CYP2E1+/+ MICE Drug Metab. Dispos., August 1, 2005; 33(8): 1144 - 1150. [Abstract] [Full Text] [PDF]

				K. Takahashi, G. E. Dinse, J. F. Foley, J. F. Hardisty, and R. R. Maronpot Comparative Prevalence, Multiplicity, and Progression of Spontaneous and Vinyl Carbamate-Induced Liver Lesions in Five Strains of Male Mice Toxicol Pathol, August 1, 2002; 30(5): 599 - 605. [Abstract] [PDF]

				K. Toyosawa, K. Okimoto, I. Kobayashi, K. Kijima, E. Kikawa, M. Kohchi, T. Koujitani, K. Tanaka, and N. Matsuoka Di(2-ethylhexyl)phthalate Induces Hepatocellular Adenoma in Transgenic Mice Carrying a Human Prototype c-Ha-ras Gene in a 26-Week Carcinogenicity Study Toxicol Pathol, June 1, 2001; 29(4): 458 - 466. [Abstract] [PDF]

				P.-G. Forkert, R. P. Lee, and K. Reid Involvement of CYP2E1 and Carboxylesterase Enzymes in Vinyl Carbamate Metabolism in Human Lung Microsomes Drug Metab. Dispos., March 1, 2001; 29(3): 258 - 263. [Abstract] [Full Text]

				A. P. Titis and P.-G. Forkert Strain-Related Differences in Bioactivation of Vinyl Carbamate and Formation of DNA Adducts in Lungs of A/J, CD-1, and C57BL/6 Mice Toxicol. Sci., January 1, 2001; 59(1): 82 - 91. [Abstract] [Full Text] [PDF]

				R. P. Lee and P.-G. Forkert Inactivation of Cytochrome P-450 (CYP2E1) and Carboxylesterase (Hydrolase A) Enzymes by Vinyl Carbamate in Murine Pulmonary Microsomes Drug Metab. Dispos., February 1, 1999; 27(2): 233 - 239. [Abstract] [Full Text]

				K. Mitsumori, H. Koizumi, T. Nomura, and S. Yamamoto Pathological Features of Spontaneous and Induced Tumors in Transgenic Mice Carrying a Human Prototype c-Ha-ras Gene Used for Six-Month Carcinogenicity Studies Toxicol Pathol, July 1, 1998; 26(4): 520 - 531. [Abstract] [PDF]

				R. W. Benson and F. A. Beland Modulation of Urethane (Ethyl Carbamate) Carcinogenicity by Ethyl Alcohol: A Review International Journal of Toxicology, November 1, 1997; 16(6): 521 - 544. [Abstract] [PDF]