Disease relevance of DIBROMOETHANE

• Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6-alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene [1].
• All treatment groups showed normal weight gain except the DBE group [2].
• DBE caused the expected high incidence of squamous carcinomas of the forestomach [2].
• Cell proliferation was examined as a measure of dibromoethane toxicity [3].

High impact information on DIBROMOETHANE

• As a result, the rate of hydrolysis of the alkyl-enzyme intermediate became the main determinant of the kcat for DBE, which was 2-fold higher than the wild-type kcat [4].
• A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates [5].
• We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases [1].
• We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity [1].
• Dibromoethane GSH conjugates also contribute to DBE cytotoxicity as depleting hepatocyte GSH beforehand increased hepatocyte resistance to DBE but not other dibromoalkanes [6].

Biological context of DIBROMOETHANE

• Dibromoethane, given by gavage and inhalation, was carcinogenic in B6C3F1 mice, F344 rats and Osborne-Mendel rats [7].
• The number of sister chromatid exchanges induced by dibromoethane was significantly lower in the fibroblasts with glutathione synthetase deficiency compared to control cells [3].
• In vitro assessment of the effect of halogenated hydrocarbons: chloroform, dichloromethane, and dibromoethane on embryonic development of the rat [8].
• TSA-IV (10), however, was synthesized from norcocaine which was protected with dibromoethane to yield 4 before acid hydrolysis, esterification and phenylphosphonylation were carried out [9].

Anatomical context of DIBROMOETHANE

• Effect of decreased glutathione levels in hereditary glutathione synthetase deficiency on dibromoethane-induced genotoxicity in human fibroblasts [3].
• In vitro bioactivation of haloethanes was mainly performed by microsomes in the case of dichloroethane and by cytosolic fractions in the case of dibromoethane [10].
• A rodent respiratory tract carcinogen, 1,2-dibromoethane (DBE), following inhalation exposure, displayed no mutagenic activity, neither in lung nor in nasal mucosa, at a single 2-h exposure to 30 ppm, which is below the highest concentration used in a NTP cancer bioassay [11].
• Slight increases were observed on the mutant frequency in the testis DNA isolated from the mice 14 days after treatment with DBCP at 40 mg/kg or with DBE at 60 mg/kg but not in the liver [12].

Associations of DIBROMOETHANE with other chemical compounds

• Respiratory pathology in rats and mice after inhalation of 1,2-dibromo-3-chloropropane or 1,2 dibromoethane for 13 weeks [13].
• Carcinogenicity of dietary dimethylnitrosomorpholine, N-methyl-N'-nitro-N-nitrosoguanidine, and dibromoethane in rainbow trout [14].
• 1,1,1,-Trichloroethane, benzene, trichloroethylene, tetrachloroethylene, dibromoethane, 1,2-dichloroethane, and 1,1,2,2-tetrachloroethane were applied to the skin of guinea-pigs for histopathological studies [15].
• Carcinogenicity bioassays of bromoacetaldehyde and bromoethanol--potential metabolites of dibromoethane [16].

References