Mechanisms of lung tumorigenesis by ethyl carbamate and vinyl carbamate.

Vinyl carbamate (VC) and ethyl carbamate (EC) induce the formation of lung tumors. The mechanism involves a two-step oxidation of EC to VC and VC to an epoxide, both of which are mediated mainly by CYP2E1. Interaction of the epoxide with DNA leads to the formation of DNA adducts, including 1,N(6)ethenodeoxyadenosine and 1,N(4)-ethenodeoxycytidine.

Inhibition of vinyl carbamate-induced lung tumors and Kras2 mutations by the garlic derivative diallyl sulfone.

Vinyl carbamate (VC) is derived from ethyl carbamate (EC), a chemical found in alcoholic beverages and fermented foods. The objectives of this study were to characterize the formation of lung tumors induced by VC in F1 (Big BluexA/J) mice, and to identify the mutations formed in the Kras2 gene. In addition, we have tested the hypothesis that pretreatment with diallyl sulfone (DASO2) inhibits the adverse effects of VC.

Trichloroethylene exposure elicits damage in epididymal epithelium and spermatozoa in mice.

We have investigated the toxic effects of trichloroethylene (TCE) on the epididymis and epididymal sperm in mice. Mice were exposed to TCE (1000 ppm) by inhalation for 6 h/day for 5 days/week for 1 to 4 weeks. Segments of the epididymis (caput, corpus and cauda) were examined by light and electron microscopy.

Inhibition of vinyl carbamate-induced mutagenicity and clastogenicity by the garlic constituent diallyl sulfone in F1 (Big Blue x A/J) transgenic mice.

Vinyl carbamate (VC) is a metabolite of ethyl carbamate (EC), a naturally occurring compound found in fermented foods and alcoholic beverages. CYP2E1 mediates the sequential oxidation of EC to VC and subsequently to the vinyl carbamate epoxide, which is believed to be the ultimate carcinogenic species. Here, we have tested the hypothesis that bioactivation of VC by CYP2E1 plays a central role in the development of its mutagenicity and clastogenicity, and further that inhibition of CYP2E1 by diallyl sulfone (DASO(2)) leads to diminution in their incidences.

Oxidation of vinyl carbamate and formation of 1,N6-ethenodeoxyadenosine in murine lung.

Vinyl carbamate (VC) is derived from ethyl carbamate, a carcinogen formed in fermentation of food and alcoholic products. We have undertaken studies to test the hypothesis that an epoxide generated from VC oxidation leads to formation of 1,N6-ethenodeoxyadenosine (epsilon dAS). We have developed approaches using liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry for identification and quantitation of epsilon dAS.