Metabolism and covalent binding of vic-dihaloalkanes, vinyl halides and acrylonitrile.
The roles of various metabolic pathways in DNA and protein alkylation are discussed here. Simple vinyl halides are oxidized to 2-haloethylene oxides and 2-haloacetaldehydes, which alkylate DNA and proteins, respectively. Polysubstituted vinyl halides are oxidized with group transfer to yield halocarbonyl compounds which alkylate proteins. Oxidation of vic-dihaloalkanes results in protein alkylation while glutathione conjugates alkylate DNA. Acrylonitrile, without previous activation, alkylates proteins and glutathione. Oxidation of acrylonitrile yields a relatively stable epoxide which can react with DNA in vitro, but alkylation by this epoxide does not occur readily in vivo. Hard-soft acid-base theory is of some use in understanding why some adducts are formed in preference to others.
D000181:Acrylonitrile / Q000378:metabolism* / Q000633:toxicity; D000241:Adenosine / Q000031:analogs & derivatives; D000818:Animals; D001711:Biotransformation; D003545:Cysteine / Q000378:metabolism; D003562:Cytidine / Q000031:analogs & derivatives; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000378:metabolism* / Q000633:toxicity; D008862:Microsomes, Liver / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism*; D014753:Vinyl Compounds / Q000378:metabolism* / Q000633:toxicity
C012962:3,N(4)-ethenocytidine; D006846:Hydrocarbons, Halogenated; D009570:Nitriles; D014753:Vinyl Compounds; C007640:1,N(6)-ethenoadenosine; D003562:Cytidine; D004247:DNA; D005978:Glutathione; D000241:Adenosine; D003545:Cysteine; D000181:Acrylonitrile