title: Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts.
abstract: Ethylene dibromide (1,2-dibromoethane, EDB) can be activated to electrophilic species by either oxidative metabolism or conjugation with glutathione. Although conjugation is generally a route of detoxication, in this case it leads to genetic damage. The major DNA adduct has been identified as S-[2-(N7-guanyl)ethyl]glutathione, which is believed to arise via half-mustard and episulfonium ion intermediates. The adduct has a half-life of about 70 to 100 hr and does not appear to migrate to other DNA sites. Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: F P
authors.initials: FP
authors.lastname: Guengerich
authors.forename: L A
authors.initials: LA
authors.lastname: Peterson
authors.forename: J L
authors.initials: JL
authors.lastname: Cmarik
authors.forename: N
authors.initials: N
authors.lastname: Koga
authors.forename: P B
authors.initials: PB
authors.lastname: Inskeep
mesh_terms: D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D015946:Ethylene Dibromide / Q000378:metabolism* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000378:metabolism*; D006846:Hydrocarbons, Halogenated / Q000378:metabolism / Q000633:toxicity; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012306:Risk
chemical_list: D002273:Carcinogens; D006842:Hydrocarbons, Brominated; D006846:Hydrocarbons, Halogenated; D015946:Ethylene Dibromide; D004247:DNA; D005978:Glutathione