Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Metabolism of the nephrotoxin dichloroacetylene by glutathione conjugation

Journal Article · · Chem. Res. Toxicol.; (United States)
DOI:https://doi.org/10.1021/tx00007a009· OSTI ID:6044118
; ;

The authors report the identification of S-(1,2-dichlorovinyl)glutathione (DCVG) as a product of the glutathione (GSH) dependent metabolism of DCA in vitro and the identification of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (N-Ac-DCVC) as a urinary metabolite of DNA in rats. Formation of DCVG from DCa, used a 1:1 complex with diethyl ether, in male rat liver and kidney subcellular fractions was dependent on time, native protein, and the presence of GSH. Initial reactions rates at 23 /degrees/C were determined as 2923 nmol/(min/times/mg) for kidney microsomes. With cytosol, DCVG formation rates were 705 nmol/(min/times/mg) (liver cytosol) and 129 nmol/(min/times/mg) (kidney cytosol). With liver microsomes, a K/sub M/ of 7.5 mM and a V/sub max/ of 5464 nmol/(min/times/mg) for GSH were obtained. The product DCVG, was definitively identified by /sup 1/H NMR spectrometry (400 MHz), mass spectrometry, and UV spectroscopy. N-Ac-DCVC was identified as a urinary metabolite from rats by GC/MS after esterification. Urine from male rats exposed to 36 /plus minus/ 5 ppm DCA for 1 h contained 10.7 ..mu..mol of N-Ac-DCVC as determined by HPLC analysis. Formation of DCVG, renal processing to S-(1,2-dichlorovinyl)-L-cysteine, and cleavage of this cysteine S-conjugate by cysteine S-conjugate ..beta..-lyase in the kidney with formation of reactive and mutagenic intermediates may account for DCA nephrotoxicity and nephrocarcinogenicity.

Research Organization:
Universitaet Wuerzburg (Germany, F.R.)
OSTI ID:
6044118
Journal Information:
Chem. Res. Toxicol.; (United States), Journal Name: Chem. Res. Toxicol.; (United States) Vol. 2:1; ISSN CRTOE
Country of Publication:
United States
Language:
English

Similar Records

Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene
Journal Article · Thu Feb 14 23:00:00 EST 2013 · Toxicology and Applied Pharmacology · OSTI ID:22285235
Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice: Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine
Journal Article · Wed Jul 01 00:00:00 EDT 2009 · Toxicology and Applied Pharmacology · OSTI ID:21272596
Role of hydrogen sulfide (H/sub 2/S) in metabolism and toxicity of cysteine S-conjugates in rat kidney
Journal Article · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) · OSTI ID:6933308

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BODY
CARCINOGENESIS
CELL CONSTITUENTS
CHLORINATED ALIPHATIC HYDROCARBONS
CHROMATOGRAPHY
DRUGS
GLUTATHIONE
HALOGENATED ALIPHATIC HYDROCARBONS
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
METABOLITES
MICROSOMES
NMR SPECTRA
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
PATHOGENESIS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SEPARATION PROCESSES
SPECTRA
TIME DEPENDENCE
TOXICITY
VERTEBRATES