Bioactivation of Nephrotoxic Haloalkenes by Glutathione Conjugation: Formation of Toxic and Mutagenic Intermediates by Cysteine Conjugate β-Lyase

The Role of Glutathione and Glutathione S-Transferases in the Metabolism of Chemical Carcinogens and Other Electrophilic Agents

1979 • 1,179 citations

Fluorine in Organic Chemistry

2004 • 1,052 citations

DETOXICATION MECHANISMS

1960 • 760 citations

Toxicology. The basic science of poisons

1976 • 758 citations

Bioactivation of foreign compounds

1985 • 733 citations

Enzymatic Basis of Detoxication

1980 • 717 citations

The origin and characteristics of a pig kidney cell strain, LLC-PK1

1976 • 604 citations

Glutathione: interorgan translocation, turnover, and metabolism.

1979 • 601 citations

Molecular structure and energetics

1986 • 573 citations

Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver.

1984 • 393 citations

Fluorine in Organic Chemistry

1974 • 300 citations

The isozymes of glutathion transferase

1985 • 293 citations

Studies on the GABA pathway—I

1961 • 287 citations

“Topics in sulfur chemistry”

1977 • 260 citations

Microsomal Glutathione S-Transferase

2005 • 247 citations

The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I. Activation through conjugation with glutathion in vitro

1978 • 247 citations

The fate of extracellular glutathione in the rat☆

1978 • 245 citations

Enzymatic Basis of Detoxication

1981 • 244 citations

Glutathione Transferases

1980 • 242 citations

Mechanism of S-(1,2-dichlorovinyl)glutathione-induced nephrotoxicity

1986 • 208 citations

A Review of the Environmental and Mammalian Toxicology of Nitrilotriacetic Acid

1985 • 208 citations

Rat liver canalicular membrane vesicles. Isolation and topological characterization.

1983 • 202 citations

Biosynthesis and biotransformation of glutathioneS-Conjugates to toxic metabolites

1988 • 193 citations

The metabolism and disposition of hexachloro-1:3-butadiene in the rat and its relevance to nephrotoxicity

1984 • 192 citations

Glutathione-degrading enzymes of microvillus membranes.

1982 • 184 citations

Renal processing of glutathione conjugates

1984 • 171 citations

Renal glutathione transport. Characteristics of the sodium-dependent system in the basal-lateral membrane.

1984 • 171 citations

Mitochondrial respiratory capacity and Na+- and K+-dependent adenosine triphosphatase-mediated ion transport in the intact renal cell.

1981 • 164 citations

Possible Toxic Factor of Trichloroethylene-extracted Soybean Oil Meal³

1959 • 158 citations

Cysteine conjugate beta-lyase in rat liver. A novel enzyme catalyzing formation of thiol-containing metabolites of drugs.

1978 • 155 citations

Structure/activity studies of the nephrotoxic and mutagenic action of cysteine conjugates of chlgro and fluoroalkenes

1985 • 154 citations

A purified cysteine conjugate beta-lyase from rat kidney cytosol. Requirement for an alpha-keto acid or an amino acid oxidase for activity and identity with soluble glutamine transaminase K.

1986 • 153 citations

Evidence for formation of an S-[2-(N7-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA.

1983 • 150 citations

Cytotoxicity of S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine in isolated rat kidney cells.

1986 • 147 citations

ISI Atlas of Science: Pharmacology

1989 • 144 citations

The colorimetric determination of γ-glutamyl transpeptidase with a synthetic substrate

1960 • 143 citations

Metabolism of glutathione and a glutathione conjugate by isolated kidney cells.

1979 • 140 citations

Microsomal glutathione transferase. Primary structure.

1985 • 136 citations

Role of microsomal and cytosolic glutathione S-transferases in the conjugation of hexachloro-1:3-butadiene and its possible relevance to toxicity.

1984 • 135 citations

Metabolism of trichloroethylene in isolated hepatocytes, microsomes, and reconstituted enzyme systems containing cytochrome P-450.

1983 • 134 citations

Bacterial β-lyase mediated cleavage and mutagenicity of cysteine conjugates derived from the nephrocarcinogenic alkenes trichloroethylene, tetrachloroethylene and hexachlorobutadiene

1986 • 133 citations

Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal mucosa and bone marrow by inhaled [14C]- and [3H]formaldehyde

1984 • 132 citations

Reactions of nucleophiles with ethylenic substrates

1971 • 132 citations

Species differences in response to trichloroethylene

1985 • 127 citations

Specificity of a particulate rat renal peptidase and its localization along with other enzymes of mercapturic acid synthesis

1978 • 124 citations

Renal cysteine conjugate beta-lyase. Bioactivation of nephrotoxic cysteine S-conjugates in mitochondrial outer membrane.

1986 • 122 citations

Novel metabolites of trichloroethylene through dechlorination reactios in rats, mice and humans

1984 • 122 citations

The inhibition of γ-glutamyl transpeptidase and glutathione metabolism of isolated rat kidney cells by L-(αS, 5S)-α-amino-3-chloro-4, 5-dihydro-5-isoxazoleacetic acid (AT-125; NSC-163501)

1980 • 120 citations

The interorgan metabolism of glutathione

1980 • 116 citations

Identification of S-1,2-dichlorovinyl-N-acetyl-cysteine as a urinary metabolite of trichloroethylene: A possible explanation for its nephrocarcinogenicity in male rats

1986 • 116 citations

Results of a two year chronic toxicity study with hexachlorobutadiene in rats

1977 • 115 citations

Intrabiliary glutathione hydrolysis. A source of glutamate in bile.

1986 • 113 citations

The acute toxic effects of hexachloro-1 : 3-butadiene on the rat kidney

1979 • 113 citations

Glutathione- and cysteine-mediated cytotoxicity of allyl and benzyl isothiocyanate

1986 • 110 citations

Chemically Induced Nephrotoxicity: Role of Metabolic Activation

1984 • 110 citations

A pathological study on the toxicity of S-dichlorovinyl-l-cysteine

1965 • 108 citations

Chemical Mechanisms of Halocarbon Metabolism

1983 • 107 citations

The metabolism and nephrotoxicity of tetrafluoroethylene in the rat

1984 • 107 citations

2,2,4-Trimethylpentane-induced nephrotoxicity

1987 • 104 citations

S-[2-(N7-guanyl)ethyl]glutathione, the major DNA adduct formed from 1,2-dibromoethane

1986 • 104 citations

The role of glutathione conjugate metabolism and cysteine conjugate beta-lyase in the mechanism of S-cysteine conjugate toxicity in LLC-PK1 cells.

1986 • 103 citations

The rich mechanistic world of nucleophilic vinylic (S_NV) substitution

1985 • 103 citations

Glutathione S‐Conjugate Formation from 1‐Chloro‐2,4‐dinitrobenzene and Biliary S‐Conjugate Excretion in the Perfused Rat Liver

1979 • 100 citations

Cleavage of S-(1,2-dichlorovinyl)-l-cysteine by an enzyme of bovine origin

1965 • 100 citations

Effect of the organic acid transport inhibitor probenecid on renal cortical uptake and proximal tubular toxicity of hexachloro-1,3-butadiene and its conjugates*1

1985 • 98 citations

Coupling of active ion transport and aerobic respiratory rate in isolated renal tubules.

1980 • 96 citations

Metabolism of dihalomethanes to formaldehyde and inorganic halide—II

1978 • 93 citations

Metabolism of haloforms to carbon monoxide—III

1979 • 93 citations

Transport of glutathione by renal basal-lateral membrane vesicles

1983 • 91 citations

The metabolism of ethylene dibromide in the rat

1970 • 91 citations

Covalent binding of 1,2-dihaloalkanes to DNA and stability of the major DNA adduct, S-[2-(N7-guanyl)ethyl]glutathione.

1986 • 91 citations

Identification of S‐1,2,2‐trichlorovinyl‐N‐acetylcysteine as a urinary metabolite of tetrachloroethylene: Bioactivation through glutathione conjugation as a possible explanation of its nephrocarcinogenicity

1986 • 91 citations

Assessment of the kidney function in maintenance of plasma glutathione concentration and redox state in anaesthetized rats

1979 • 89 citations

Chloroacetylenes as Michael acceptors. 3. Mechanism and synthetic utility of enolate reactions with halogenated olefins and chloroacetylenes

1984 • 87 citations

Hydrocarbon Nephropathy in Male Rats: Identification of the Nephrotoxic Components of Unleaded Gasoline

1985 • 86 citations

Bioactivation of tetrachloroethylene. Role of glutathione S-transferase-catalyzed conjugation versus cytochrome P-450-dependent phospholipid alkylation.

1987 • 82 citations

Thioacylating intermediates as metabolites of S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2,2-trichlorovinyl)-L-cysteine formed by cysteine conjugate .beta.-lyase

1988 • 81 citations

Uptake of the glutathione conjugate S-(1,2-dichlorovinyl)glutathione by renal basal-lateral membrane vesicles and isolated kidney cells.

1985 • 79 citations

Absorption, elimination and metabolism of trichloroethylene: a quantitative comparison between rats and mice

1986 • 79 citations

Nephrotoxicity of S-(2-chloro-1,1,2-trifluoroethyl)glutathione and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine, the glutathione and cysteine conjugates of chlorotrifluoroethene.

1985 • 77 citations

Isolation and characterization of a rat liver enzyme with both cysteine conjugate beta-lyase and kynureninase activity.

1985 • 76 citations

Assay of cysteine conjugate β-lyase activity with S-(2-benzothiazolyl)cysteine as the substrate

1982 • 76 citations

Differentiation of the mechanisms of oncogenicity of 1,4-dioxane and 1,3-hexachlorobutadiene in the rat

1981 • 75 citations

Immunocytochemical localization of gamma-glutamyltransferase in rat kidney with protein A-horseradish peroxidase.

1982 • 73 citations

Enzymes of Mercapturic Acid Formation

1980 • 73 citations

The role of mitochondrial matrix enzymes in the metabolism and toxicity of cysteine conjugates.

1988 • 71 citations

Enzymatic transformation of mercapturic acids derived from halogenated alkenes to reactive and mutagenic intermediates

1987 • 71 citations

Formation and metabolism of a glutathione-S-conjugate in isolated rat liver and kidney cells

1978 • 70 citations

Cysteine S-conjugate N-acetyltransferase from rat kidney microsomes.

1982 • 70 citations

Mutagenicity of amino acid and glutathione S-conjugates in the Ames test

1988 • 69 citations

The mechanism of pentachlorobutadienyl-glutathione nephrotoxicity studied with isolated rat renal epithelial cells

1986 • 66 citations

Direct evidence for the role of the membrane potential in glutathione transport by renal brush-border membranes.

1985 • 64 citations

Effects of inhaled chlorotrifluoroethylene and hexafluoropropene on the rat kidney

1981 • 62 citations

Hepato-Renal Cooperation in Biotransformation, Membrane Transport, and Elimination of Cysteine S -Conjugates of Xenobiotics 1

1984 • 62 citations

Purification and characterization of C-S lyase from Fusobacterium varium. A C-S cleavage enzyme of cysteine conjugates and some S-containing amino acids.

1984 • 61 citations

Blood Dyscrasia in Calves Induced by S-(Dichlorovinyl)-L-Cysteine

1959 • 60 citations

Renal transport processes and glutathione conjugate-mediated nephrotoxicity.

1987 • 59 citations

Urinary Metabolites of 14C-Tetrachloroethylene in Mice

1961 • 59 citations

Bioactivation mechanism of the cytotoxic and nephrotoxic S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine.

1987 • 57 citations

Stereospecific Reactions of Nucleophilic Agents with Acetylenes and Vinyl-type Halides. I. The Mechanism of the Base-catalyzed Reaction of cis-Dichloroethylene with Thiols¹

1956 • 56 citations

In vivoandin vitronephrotoxicity of the cysteine conjugate of hexachlorobutadiene

1983 • 56 citations

The Free Radical Addition of Hydrogen Sulfide to Fluoroethylenes

1963 • 56 citations

Short-term toxicity and reproduction studies in rats with hexachloro-(1,3)-butadiene

1979 • 55 citations

A mechanism of S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-l-cysteine toxicity to rabbit renal proximal tubules

1987 • 55 citations

Ion regulation, cell injury and carcinogenesis

1987 • 52 citations

Reaktionen von Polychlor‐1,3‐butadienen und Polychlorbutenen mit Thiolaten

1981 • 52 citations

Evidence for the renal paratubular transport of glutathione

1982 • 52 citations

Properties of DNA treated with S-(1,2-dichlorovinyl)-l-cysteine and a lyase

1972 • 49 citations

Metabolic activation and detoxication of nephrotoxic cysteine and homocysteine S-conjugates.

1986 • 48 citations

Nephrotoxicity and hepatotoxicity of 1,1-dichloro-2,2-difluoroethylene in the rat

1987 • 46 citations

Enzymic reaction of chlorotrifluoroethene with glutathione: fluorine-19 NMR evidence for stereochemical control of the reaction

1985 • 46 citations

Metabolic Coordination of Liver and Kidney in Mercapturic Acid Biosynthesis In Vivo

1982 • 45 citations

The enzymatic reaction of chlorotrifluoroethylene with glutathione

1982 • 44 citations

Biologically active intermediates generated by the reduced glutathione conjugation pathway

1986 • 44 citations

The role of glutathione turnover in the apparent renal secretion of cystine.

1981 • 43 citations

Thioacylating agents as ultimate intermediates in the β-lyase catalysed metabolism of S-(pentachlorobutadienyl)-L-cysteine

1988 • 43 citations

Mercapturic acid formation is an activation and intermediary step in the metabolism of hexachlorobutadiene

1986 • 42 citations

Cellular effects of reactive intermediates: Nephrotoxicity of S-conjugates of amino acids

1987 • 41 citations

Structure-nephrotoxicity relationships of S-(2-chloroethyl)-DL-cysteine and analogs: role for an episulfonium ion.

1985 • 41 citations

Carcinogenicity of dichloroacetylene: an inhalation study

1984 • 40 citations

Nephrotoxicity of S-(2-chloroethyl)glutathione in the Fischer rat: evidence for gamma-glutamyltranspeptidase-independent uptake by the kidney.

1987 • 40 citations

Chronic toxicity of S‐(trans‐1,2‐dichlorovinyl)‐L‐cysteine in mice

1984 • 40 citations

Enzymatic conjugation of hexachloro-1,3-butadiene with glutathione. Formation of 1-(glutathion-S-yl)-1,2,3,4,4-pentachlorobuta-1,3-diene and 1,4-bis(glutathion-S-yl)-1,2,3,4-tetrachlorobuta-1,3-diene.

1988 • 40 citations

The formation of both a mono- and a bis-substituted glutathione conjugate of hexachlorobutadiene by isolated hepatocytes and following in vivo administration to the rat

1985 • 39 citations

Bacterial cysteine conjugate β-lyase and the metabolism of cysteine S-conjugates: Structural requirements for the cleavage of S-conjugates and the formation of reactive intermediates

1988 • 38 citations

Transport of N-acetyl-S-pentachloro-1,3-butadienylcysteine by rat renal cortex

1986 • 38 citations

Cysteine conjugate beta-lyase in the gastrointestinal bacterium Eubacterium limosum.

1986 • 38 citations

Mechanism of renal peritubular extraction of plasma glutathione

1986 • 38 citations

Generation and inhalation toxicity of dichloroacetylene

1975 • 37 citations

Thioketen‐Synthesen, VI. Stabile Thioketene durch Schwefelung sterisch gehinderter Acylchloride

1982 • 37 citations

Evidence for the active renal secretion of s-pentachlorophenyl-N-acetyl-L-cysteine by female rats

1983 • 37 citations

Methylthlolated Metabolites

1983 • 35 citations

Trichloroethylene in Organic Synthesis: I. A New, Catalytic Synthesis of Dichloroacetylene

1984 • 34 citations

Mutagenicity of hexachloro-1,3-butadiene and its S-conjugates in the Ames test—role of activation by the mercapturic acid pathway in its nephrocarcinogenicity

1988 • 34 citations

Excretion pattern and metabolism of hexachlorobutadiene in rats

1985 • 33 citations

Glutathione S‐conjugates stimulate ATP hydrolysis in the plasma membrane fraction of rat hepatocytes

1985 • 32 citations

(Na+,K+)-ATPase kinetics within the intact renal cell. The role of oxidative metabolism.

1982 • 32 citations

Stereochemistry of the glutathione-dependent biotransformation of vicinal-dihaloalkanes to alkenes.

1982 • 32 citations

Metabolism of hexachloro-1,3-butadiene in mice:in vivoandin vitroevidence for activation by glutathione conjugation

1988 • 31 citations

The pathogenesis of renal cortical tumours in rats fed 2% trisodium nitrilotriacetate monohydrate

1982 • 28 citations

Topology and some properties of the renal brush border membrane-bound peptidase(s) participating in the metabolism of S-carbamidomethyl glutathione

1981 • 27 citations

Differentiation of Genetic Versus Epigenetic Mechanisms of Toxicity and Its Application to Risk Assessment

1982 • 27 citations

Fluoride ion excretion by male rats after inhalation of one of several fluoroethylenes or hexafluoropropene

1974 • 26 citations

Formation of S-[2-(N7-guanyl)ethyl] adducts by the postulated S-(2-chloroethyl)cysteinyl and S-(2-chloroethyl)glutathionyl conjugates of 1,2-dichloroethane

1987 • 26 citations

The metabolism of 35S-(1,2-Dichlorovinyl)-l-cysteine in the calf

1963 • 22 citations

Properties of DNA isolated from tissues of calves treated with S-(1,2-dichlorovinyl)-l-cysteine

1971 • 21 citations

Presence of γ-glutamyltransferase in the renal microvascular compartment

1981 • 21 citations

Role of plasma albumin in renal elimination of a mercapturic acid

1985 • 20 citations

Aliphatische Thiocarbonsäurechloride. Darstellung und Eigenschaften

1975 • 18 citations

Metabolism and excretion of S-conjugates derived from hexachlorobutadiene in the isolated perfused rat kidney.

1988 • 17 citations

Nephrotoxic Amino Acid and Glutathione S-Conjugates: Formation and Renal Activation

1986 • 15 citations

Regulation of a S(trans‐1,2‐dichlorovinyl)‐<scp>L</scp>‐cysteine‐induced renal tubular toxicity by glutathione

1983 • 14 citations

Genotoxic and Mutagenic Assays of Halothane Metabolites in Bacillus subtilis and Salmonella typhimurium

1980 • 11 citations

γ-Glutamyltransferase in Glomeruli and Tubules of Rat Kidney Cortex: Effect of Experimental Diabetes

1980 • 11 citations

Untersuchungen zum Wirkungsmechanismus von S‐(Dichlorvinyl)‐L‐Cystein

1983 • 10 citations

Role of metabolic activation in the toxicity of S-(pentachlorobutadienyl)glutathione and in the isolated perfused rat kidney

1988 • 9 citations

Comparative defluorination and cytochrome P-450 loss by the microsomal metabolism of fluoro- and fluorochloroethenes.

1987 • 8 citations

Non-enzymatic transamination and β-elimination of<scp>DL</scp>-S-benzylcysteine catalysed by a potent pyridoxal model

1985 • 8 citations

The Reaction of o-Benzenedithiol with Hexachlorobutadiene

1980 • 6 citations