The studies to be carried out under this limited-scope application are a continuation of our previous and current studies on the electrophilic (active) and non-electrophilic (inactive) metabolites of three selected groups of chemical carcinogens and their DNA adducts. 1. The first group consists of ethyl carbamate, vinyl carbamate, vinyl carbamate epoxide, and the related human liver carcinogen, vinyl chloride and its epoxide. Considerable medical exposure of Japanese patients to ethyl carbamate occurred unwittingly in Japan from 1950 to 1975. Humans are also exposed to very low to low dietary levels of ethyl carbamate present in many foods and beverages derived from ethanolic fermentations. We wish to study the metabolism and DNA adducts of these hepatic carcinogens in rodent and human tissues. 2. The second group consists of the asarones and the precocenes that occur naturally in certain spice herbs and in certain plants as insecticides, respectively. Our previous work has included detailed studies of specific allylbenzenes (safrole, estragole, and methyl eugenol) that occur in many spice herbs. These compounds are activated via hydroxylation of the benzylic carbon followed by esterification to form electrophilic sulfuric acid esters. The asarones and the precocenes are propenylbenzenes. Our initial work suggests that the hydroxylation-ester pathway apparently does not apply to these compounds. We particularly wish to study the probable electrophilic epoxide metabolites and DNA adducts of these compounds. 3. The third group consists of the carcinogens S-vinyl-homocysteine (vinthionine) and S-ethyl-homocysteine (ethionine). They appear to have interesting differences in activation in carcinogenesis and in mutagenic properties. Our previous work included the first synthesis and discovery of the carcinogenicity and mutagenicity of vinthionine.
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