title: Metabolic activation of vinyl chloride, formation of nucleic acid adducts and relevance to carcinogenesis.
abstract: Comparative experiments with vinyl chloride and 2,2'-dichlorodiethyl ether confirm that chloroacetaldehyde, which is formed during metabolism of both compounds, binds covalently to proteins, but not to nucleic acids. The putative nucleic-acid-binding agent, chloroethylene oxide, is formed from vinyl chloride, not from 2,2'-dichlorodiethyl ether. The degree of potential carcinogenicity of epoxides formed from substituted ethylenes is considered to be determined by factors of stability/reactivity and by the rate of breakdown of epoxide and the rate of its formation. Hence, pharmacokinetic data are of considerable importance in assessing the comparative carcinogenic potencies of ethylene derivatives.
mesh_terms: D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004852:Epoxy Compounds / Q000378:metabolism; D005027:Ethylene Oxide / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014752:Vinyl Chloride / Q000378:metabolism*; D014753:Vinyl Compounds / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D004852:Epoxy Compounds; D011506:Proteins; D014753:Vinyl Compounds; C015061:chloroethylene oxide; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D005027:Ethylene Oxide; D014752:Vinyl Chloride