In vivo mutagenicity of vinyl carbamate and ethyl carbamate in lung and small intestine of F-1 (Big Blue (R) x A/J) transgenic mice

Vinyl carbamate (VC) is a metabolite of ethyl carbamate (EC), a chemical found in alcoholic beverages and fermented foods. We undertook this study to: (i) evaluate the ability of both EC and VC to induce gene mutations in lung and various extrapulmonary tissues, and (ii) identify the type of mutations induced by the two compounds in various tissues. F-1 (Big Blue((R)) X A/J) transgenic mice harboring the lambda ell transgene were used for identification and quantitation of mutations in vivo. Time-course studies in lung showed a plateau in mutant frequency (MF) 4 weeks after VC treatment, at which time mutations were fixed and were about 4-fold higher than in controls. Dose-dependent increases in MF were detected in the lung and small intestine (SI) after treatment with 15-75 mg/kg, i.p., of VC. VC was mutagenic in the lung and SI at doses of 45, 60 and 75 mg/kg. Sequencing of the cII gene in lung and SI showed that VC induced mainly A:T -> G:C transitions and A:T -> T:A transversions. EC was also mutagenic in the lung at 500 and 1,000 mg/kg and elicited mainly G:C -> A:T transitions. A VC dose of 60 mg/kg elicited a similar level of MF as an EC dose of 1,000 mg/kg. At 4 weeks after treatment, neither VC nor EC elicited mutations in the colon, bone marrow or kidney. These results demonstrated that VC and EC are mutagenic in vivo and affirm that VC is a more potent mutagen than EC. (c) 2007 Wiley-Liss, Inc.