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Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts

Journal Article · · Environ. Health Perspect.; (United States)
DOI:https://doi.org/10.1289/ehp.877615· OSTI ID:5129789
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-(N/sup 7/-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.
Research Organization:
Vanderbilt Univ. School of Medicine, Nashville, TN (USA)
OSTI ID:
5129789
Journal Information:
Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 76; ISSN EVHPA
Country of Publication:
United States
Language:
English