Disease relevance of Perchlorobutadiene

• The mutagenicity of hexachloro-1,3-butadiene and its S-conjugates 1-(glutathion-S-yl)-1,2,3,4,4-pentachloro-1,3-butadiene (GTB), 1,4-(bis-glutathion-S-yl-1,2,3,4-tetrachloro-1,3-butadiene (BGTB) and 1,4-(bis-cystein-S-yl)-1,2,3,4-tetrachloro-1,3-butadiene (BCTB) was investigated in Salmonella typhimurium TA100 using a modified preincubation assay [1].
• Chronic toxicity and reproduction studies of hexachlorobutadiene in rats [2].
• Hexachlorobutadiene induced in situ cutaneous necrosis and its absorption induced systemic damage (fatty liver degeneration and epithelial necrotizing nephritis) [3].
• We studied the response of urinary protein overload on preexisting tubulointerstitial nephritis (TIN), which was induced in male Sprague Dawley rats by hexachloro-1,3-butadiene (HCBD) [4].

High impact information on Perchlorobutadiene

• Human microsomal glutathione S-transferase. Its involvement in the conjugation of hexachlorobuta-1,3-diene with glutathione [5].
• These studies show that PCBC, a metabolite of the nephrocarcinogen hexachloro-1,3-butadiene, has important effects on mitochondrial macromolecule synthesis and on the mitochondrial genome [6].
• The sulfoxidation of the hexachlorobutadiene metabolite N-acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine is catalyzed by human cytochrome P450 3A enzymes [7].
• The sulfoxidation of the mercapturic acid N-acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (N-Ac-PCBC), a urinary metabolite of the renal toxin hexachlorobutadiene (HCBD), was studied in human liver microsomes and with purified cDNA expressed human liver cytochrome P450 (P450) enzymes [7].
• Formation of S-conjugates (identified by NMR and mass spectrometry) could be demonstrated with trichloroethene, tetrachloroethene, hexachlorobutadiene, perfluoropropene, trichlorotrifluoropropene, and dichloroacetylene in incubations with rat liver microsomes and in the isolated perfused rat liver [8].

Chemical compound and disease context of Perchlorobutadiene

• Isolated renal epithelial cells were used to study the mechanism of toxicity of pentachlorobutadienyl-glutathione (PCBG), a nephrotoxic glutathione conjugate of hexachlorobutadiene [9].
• On the basis of these quantitative data, potency ratios indicated that irritation and kidney injury are the primary manifestations of toxicity associated with short-term exposure to DCB and HCBD, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• 3. The target cell toxicity in vivo of adriamycin, 2-bromoethanamine and hexachlorobutadiene N-acetyl cysteine conjugate is selectively maintained towards glomerular epithelial, medullary interstitial and proximal tubular cells, respectively, in vitro, showing that the "in vivo-in vitro gap" can be bridged [11].
• This paper discusses some of the advantages and disadvantages of isolated cell preparations for studies of cytotoxicity and summarizes the results of recent work in which isolated hepatocytes and renal epithelial cells have been used to examine the metabolism and toxicity of menadione and hexachloro-1,3-butadiene [12].

Biological context of Perchlorobutadiene

• Excretion pattern and metabolism of hexachlorobutadiene in rats. Evidence for metabolic activation by conjugation reactions [13].
• The formation of this Michael acceptor may contribute to sex differences in hexachlorobutadiene nephrotoxicity [14].
• Hence, at moderate hexachlorobutadiene infusion rates, PCBG is exclusively excreted into bile, indicating that intestinal absorption of PCBG or its metabolites is required for the induction of kidney damage in vivo [15].
• Transfection of LLC-PK1 cells with human mGST genes resulted in increased expression of mGST protein in microsomal fractions, in increased glutathione S-conjugate formation with hexachloro-1,3-butadiene and 1-chloro-2,4-dinitrobenzene as the substrates, and in increased cytotoxicity of hexachloro-1,3-butadiene [16].
• Hexachloro-1,3-butadiene: toxicology, metabolism, and mechanisms of toxicity [17].

Anatomical context of Perchlorobutadiene

• Cysteine conjugate beta-lyase of rat kidney cytosol: characterization, immunocytochemical localization, and correlation with hexachlorobutadiene nephrotoxicity [18].
• The subcellular mechanism of alkenyl halide S-conjugate-induced nephrotoxicity was studied in mitochondria isolated from rat kidney cortex in vitro using the cysteine conjugate of hexachloro-1,3-butadiene, i.e., S-pentachlorobutadienyl-L-cysteine (PCBC) as a model substrate [19].
• Development of newly formed nephrons in the goldfish kidney following hexachlorobutadiene-induced nephrotoxicity [20].
• 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 [21].
• Induction of morphological transformation and unscheduled DNA synthesis in Syrian hamster embryo fibroblasts by hexachlorobutadiene and its putative metabolite pentachlorobutenoic acid [22].

Associations of Perchlorobutadiene with other chemical compounds

• Intestinal absorption of S-(pentachlorobutadienyl)glutathione and S-(pentachlorobutadienyl)-L-cysteine, the glutathione and cysteine S-conjugates of hexachlorobuta-1,3-diene [23].
• Acute and chronic effects of hexachlorobenzene and hexachlorobutadiene in red swamp crayfish (Procambarus clarki) and selected fish species [24].
• The MAL required for eliciting a 50% decrease in G6-phosphatase staining intensity in DCB-exposed mice was 598 ppm and that associated with 50% of damaged tubules in HCBD-exposed mice was 7.2 ppm [10].
• Acrolein and hexachlorobutadiene produced depletion in the absence of prior activation, as did menadione but for which enzyme induction increased the magnitude of depletion [25].
• Renal, biliary, pulmonary and faecal excretion experiments were carried out with labelled hexachloro-1,3-butadiene [( 14C]HCBD) in male Sprague-Dawley rats, given orally (p.o.) and intravenously (i.v.) in doses of 1 and 100 mg kg-1 as a solution in polyethylene glycol [26].

Gene context of Perchlorobutadiene

• Binding of hexachlorobutadiene to alpha 2u-globulin and its role in nephrotoxicity in rats [27].
• Glutathione reductase activity in the renal cortex of male rats treated with 200 mg/kg hexachloro-1,3-butadiene (HCBD) was inhibited as early as 1 hour after dosing, before signs of marked morphological damage [28].
• Chloroform is discussed as an example of cytochrome P-450-mediated activation and dihaloethanes and hexachloro-1,3-butadiene as examples of glutathione conjugation followed by activation [29].
• Hexachloro-1,3-butadiene (HCBD) produced a time- and dose-related increase in hepatic water content following i.p. administration to male Alderley Park (Alpk/AP) mice [30].
• Renal tissue biomarkers (glutamine synthetase and p-aminohippuric acid uptake) were studied in male and female rats after treatment with hexachloro-1,3-butadiene [31].

Analytical, diagnostic and therapeutic context of Perchlorobutadiene

• In another series of experiments, rats were killed 24 h after treatment with hexachloro- 1,3-butadiene (HCBD) [32].
• Male Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg-1 labelled hexachloro-1,3-butadiene ([14C]HCBD) by gavage 1 h (BDC1 rats) or 24 h (BDC24 rats) after surgical cannula implantation [33].
• Five positive compounds (1,2-dibromo-3-chloropropane, 1,2-dibromoethane, 1,2-dichloroethane, vinyl bromide and hexachloro-1,3-butadiene) were analyzed for a quantitative relationship between carcinogenic potency in rats and the potency of response in the Ara mutagenicity test [34].
• Determination of hexachloro-1,3-butadiene in spinach, eggs, fish, and milk by electron capture gas-liquid chromatography [35].
• Individual serum or plasma bile acid concentrations were measured by high performance liquid chromatography in two groups of workers with differing exposures: to hexachlorobutadiene (HCBD) and a mixture of other chlorinated solvents (SOLVENT) in study A; and trichloroethylene (TCE) in study B [36].

References