Disease relevance of sym-Dibromoethane

• 1,2-Dibromoethane was the only compound that induced a significant incidence (p less than 0.05) of skin papillomas, skin carcinomas, and lung tumors by repeated skin application [1].
• Paradoxical enhancement of the toxicity of 1,2-dibromoethane by O6-alkylguanine-DNA alkyltransferase [2].
• The presence of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) paradoxically increases the mutagenicity and cytotoxicity of 1,2-dibromoethane (DBE) in Escherichia coli [2].
• Integration of trapping and desorption methods with the Salmonella microsuspension bioassay was demonstrated with EDB and 4-NB recoveries from air; chemical analysis and bioassay gave comparable results (within 10%) [3].
• Experiments were designed to investigate the expression of three cell-cycle-dependent proto-oncogenes in response to two different types of proliferative stimuli: compensatory cell proliferation after partial hepatectomy (PH) or CCl4 and liver hyperplasia induced by the mitogens ethylene dibromide (EDB) and cyproterone acetate (CPA) [4].

High impact information on sym-Dibromoethane

• The binding of EDB to these macromolecules was augmented with increasing concentrations of microsomes [5].
• The binding of EDB or EDC with proteins was not significant when denatured microsomes were used or when DNA was used in the absence of microsomes [5].
• In studies carried out with isolated hepatocytes, equimolar amounts of 1,2-dibromoethane and endogenous GSH were also bound to intracellular DNA and RNA and extracellular DNA [6].
• Enzymatic hydrolysis of calf thymus DNA labeled with 1,2-dibromoethane in the presence of GSH and GSH S-transferase and subsequent high-performance liquid chromatography of the residues yielded a major fraction, which also was found to contain radiolabel derived from GSH [6].
• The major DNA adduct formed from the carcinogen ethylene dibromide (1,2-dibromoethane, EDB) is S-[2-(N7-guanyl)ethyl]glutathione, resulting from the reaction of guanyl residues with the half-mustard S-(2-bromoethyl)glutathione, which is generated by glutathione S-transferase-catalyzed conjugation of EDB with glutathione [7].

Chemical compound and disease context of sym-Dibromoethane

• 1,2-Dibromoethane and 1,2-dibromo-3-chloropropane caused stomach tumors with many metastases in both rats and mice [8].
• 1. Toxicity of 1,2-dibromoethane requires bioactivation via glutathione S-transferase [9].
• This review summarizes the effects of the alpha1-adrenergic agonist, phenylephrine, at enhancing the toxicity of 2-bromohydroquinone, 1,2-dibromoethane, and cis-diammineplatinum(II) dichloride [10].

Biological context of sym-Dibromoethane

• Characterization of the hepatic DNA damage caused by 1,2-dibromoethane using the alkaline elution technique [11].
• Bromoaldehydic metabolites formed by cytochrome P450-dependent mixed-function oxidases were probably responsible for lipid peroxidation as deuterated 1,2-dibromoethane (d4-DBE) induced less lipid peroxidation and was less cytotoxic even though GSH was depleted as rapidly and as effectively [12].
• Metabolic activation of 1,2-dibromoethane to a free radical intermediate by rat liver microsomes and isolated hepatocytes [13].
• Conjugative metabolism of 1,2-dibromoethane in mitochondria: disruption of oxidative phosphorylation and alkylation of mitochondrial DNA [14].
• 1,2-Dibromoethane-induced cell proliferation is not a regenerative response because at the dose used in this study, no tubular necrosis was observed by histologic examination [15].

Anatomical context of sym-Dibromoethane

• Enhancement of BALB/c 3T3 cells transformation by 1,2-dibromoethane promoting effect [16].
• Induction of DNA repair in rat spermatocytes and hepatocytes by 1,2-dibromoethane: the role of glutathione conjugation [17].
• Ethylene dibromide (1,2-dibromoethane; EDB) was tested for the induction of dominant lethal and electrophoretically-detectable specific-locus mutations in the germ cells of DBA/2J male mice [18].
• The combination of 1,2-dibromoethane (DBE) with carbon tetrachloride (CCl4) in the isolated rat hepatocyte model produces a significant potentiation of both lipid peroxidation and plasma membrane damage induced by the latter compound [19].
• After incubation of 14C-labelled 1,2-dibromoethane or chloroform with homogenates prepared from rat conjunctiva, the presence of irreversibly protein-bound radioactivity was detected [20].

Associations of sym-Dibromoethane with other chemical compounds

• Liver AP-1 activation due to carbon tetrachloride is potentiated by 1,2-dibromoethane but is inhibited by alpha-tocopherol or gadolinium chloride [21].
• Intraperitoneal administration of 0.5 mmol/kg of 1-bromo-2-chloroethane and 1,2-dibromoethane produced similar levels of DNA damage [22].
• O(6)-Alkylguanine DNA-alkyl transferase (AGT) has been shown to conjugate both 1,2-dibromoethane and dibromomethane, yielding AGT inactivation, DNA-AGT cross-linking, and enhanced mutagenicity [23].
• 1,2-Dichloroethane (DCE) and 1,2-dibromoethane (DBE) were tested for the ability to induce gene mutations in two human lymphoblastoid cell lines, designated AHH-1 and TK6 [24].
• Lipid peroxidation and irreversible cell damage: synergism between carbon tetrachloride and 1,2-dibromoethane in isolated rat hepatocytes [19].

Gene context of sym-Dibromoethane

• Ethylene dibromide (1,2-dibromoethane, EDB) is metabolized by two routes: a conjugative route catalyzed by glutathione S-transferases (GST) and an oxidative route catalyzed by cytochrome P450 (P450) [25].
• The 1,2-dibromoethane-degrading strain GP1 contained a conserved DNA segment of 2.7 kb, which included dhaR, dhaA, and part of invA [26].
• 1,2-Dibromoethane (EDB) is a widely used industrial chemical, and a well-known mutagen and carcinogen [17].
• In addition, elevated expression of c-myc was found only in liver hyperplasia induced by EDB, but not with CPA [4].
• The expression of the DNA repair protein human O(6)-alkylguanine-DNA alkyltransferase (AGT) in Escherichia coli strains GWR109 or TRG8 that lack endogenous AGT greatly increased the toxicity and mutagenicity of 1,2-dibromoethane (DBE) [27].

Analytical, diagnostic and therapeutic context of sym-Dibromoethane

• In vivo experiments with DBCP yielded very low levels of the N7-guanyl adducts formed in rat liver compared to the levels seen after treatments with 1,2-dibromoethane [28].
• The temperature optimum of DmbA and DmbB proteins determined with 1,2-dibromoethane is 45 degrees C. The melting temperature assessed by circular dichroism spectroscopy of DmbA is 47 degrees C and DmbB is 57 degrees C. The pH optimum of DmbA depends on composition of a buffer with maximal activity at 9 [29].
• A one-electron reductive metabolism of 1,2-dibromoethane (DBE) is described that gives rise to a free radical intermediate, which can be stabilized by a spin trapping agent and detected by electron spin resonance spectroscopy [13].
• Diethylmaleate (DEM) potentiated the 1,2-dibromoethane (DBE)-induced hepatic morphological lesion in fasted male Wistar rats, as revealed by light and electron microscopy examination [30].
• Quantitative analysis of embryonic kidney impairment by confocal microscopy and stereology: effect of 1,2-dibromoethane in the chick mesonephros [31].

References