Glutathione‐dependent Bioactivation of Haloalkanes and Haloalkenes
- 1 January 2004
- journal article
- review article
- Published by Taylor & Francis in Drug Metabolism Reviews
- Vol. 36 (3-4) , 583-594
- https://doi.org/10.1081/dmr-200033451
Abstract
Haloalkanes and haloalkenes constitute an important group of widely used chemicals that have the potential to induce toxicity and cancer. The toxicity of haloalkanes and haloalkenes may be associated with cytochromes P450- or glutathione transferase-dependent bioactivation. This review is concerned with the glutathione- and glutathione transferase-dependent bioactivation of dihalomethanes, 1,2-dihaloalkanes, and haloalkenes. Dihalomethanes, e.g., dichloromethane, and 1,2-dihaloethanes, e.g., 1,2-dichloroethane and 1,2-dibromoethane, undergo glutathione transferase-catalyzed bioactivation to give S-(halomethyl)glutathione or glutathione episulfonium ions, respectively, as reactive intermediates. Haloalkenes, e.g., trichloroethene, hexachlorobutadiene, chlorotrifluoroethene, and tetrafluoroethene, undergo cysteine conjugate beta-lyase-dependent bioactivation to thioacylating intermediates, including thioacyl halides, thioketenes, and 2,2,3-trihalothiiranes. With all of these compounds, the formation of reactive intermediates is associated with their observed toxicity.Keywords
This publication has 54 references indexed in Scilit:
- Toxic, halogenated cysteine S-conjugates and targeting of mitochondrial enzymes of energy metabolismBiochemical Pharmacology, 2002
- Role of cytochrome P450 and glutathione S-transferase α in the metabolism and cytotoxicity of trichloroethylene in rat kidneyBiochemical Pharmacology, 2000
- GLUTATHIONE-DEPENDENT BIOACTIVATION OF HALOALKENESAnnual Review of Pharmacology and Toxicology, 1998
- Dichloromethane Metabolism to Formaldehyde and Reaction of Formaldehyde with Nucleic Acids in Hepatocytes of Rodents and Humans with and without GlutathioneS-TransferaseT1andM1GenesFundamental and Applied Toxicology, 1997
- Bioactivation of S-(2,2-Dihalo-1,1-difluoroethyl)-l- cysteines and S-(Trihalovinyl)-l-cysteines by Cysteine S-Conjugate β-Lyase: Indications for Formation of both Thionoacylating Species and Thiiranes as Reactive IntermediatesChemical Research in Toxicology, 1996
- Isolation from Rat Kidney of a Cytosolic High Molecular Weight Cysteine-S-Conjugate β-Lyase with Activity toward Leukotriene E4Journal of Biological Chemistry, 1995
- Nephrotoxicity of mercapturic acids of three structurally related 2,2-difluoroethylenes in the ratBiochemical Pharmacology, 1988
- Effects of AT-125 on the nephrotoxicity of hexachloro-1,3-butadiene in ratsToxicology and Applied Pharmacology, 1988
- Bioactivation mechanism of the cytotoxic and nephrotoxic S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine.Proceedings of the National Academy of Sciences, 1987
- Metabolism of dihalomethanes to formaldehyde and inorganic halide—IIBiochemical Pharmacology, 1978