Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts.

Guengerich FP, Peterson LA, Cmarik JL, Koga N, Inskeep PB
Environ Health Perspect. 1987 76: 15-8

PMID: 3329096 · PMCID: PMC1474475 · DOI:10.1289/ehp.877615

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.

MeSH Terms (12)

Animals Carcinogens DNA DNA Damage Ethylene Dibromide Glutathione Humans Hydrocarbons, Brominated Hydrocarbons, Halogenated In Vitro Techniques Liver Risk

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