Trapping and identification of the dichloroacetate radical from the reductive dehalogenation of trichloroacetate by mouse and rat liver microsomes
| Autor: | Irvin R. Schultz, Richard J. Bull, J. L. Merdink |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Dichloroacetic Acid Free Radicals Chemistry Stereochemistry Radical Metabolite Halogenation Mice Inbred Strains Reaction intermediate Condensation reaction Biochemistry Rats Inbred F344 Rats Adduct Lipid peroxidation Mice chemistry.chemical_compound Models Chemical Physiology (medical) Microsomes Liver Microsome Animals Trichloroacetic Acid Oxidation-Reduction |
| Zdroj: | Free Radical Biology and Medicine. 29:125-130 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/s0891-5849(00)00330-0 |
| Popis: | A key question in the risk assessment of trichloroethylene (TRI) is the extent to which its carcinogenic effects might depend on the formation of dichloroacetate (DCA) as a metabolite. One of the metabolic pathways proposed for the formation of DCA from TRI is by the reductive dehalogenation of trichloroacetate (TCA), via a free radical intermediate. Although proof of this radical has been elusive, the detection of fully dechlorinated metabolites in the urine and the formation of lipid peroxidation by-products in microsomal incubations with TCA argue for its existence. We report here the trapping of the dichloroacetate radical with the spin-trapping agent PBN, and its identification by GC/MS. The PBN/dichloroacetate radical adduct was found to undergo an intramolecular rearrangement during its extraction into organic solvent. An internal condensation reaction between the acetate and the nitroxide radical moieties is hypothesized to form a cyclic adduct with the elimination of an OH radical. The PBN/dichloroacetate radical adduct has been identified by GC/MS in both a chemical Fenton system and in rodent microsomal incubations with TCA as substrate. |
| Databáze: | OpenAIRE |
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