Disease relevance of CHLOROETHYLENE OXIDE

• Chloroethylene oxide-modified poly(deoxyguanylate-deoxycytidylate) was assayed as template in a replication fidelity assay with Escherichia coli DNA polymerase I, and the newly synthesized product was subjected to nearest-neighbor analysis [1].
• Both features support the evidence linking vinyl chloride exposure to hepatic angiosarcomas containing an increased frequency of p53 mutations with a mutational spectrum (i.e. A:T --> T:A transversions) characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride [2].
• Mutagenicity and toxicity of chloroethylene oxide and chloroacetaldehyde [3].

High impact information on CHLOROETHYLENE OXIDE

• Chloroethylene oxide was found to be the most effective in inducing forward mutations in Sch. pombe and gene conversions in S. cerevisiae, increasing the mutation and conversion frequencies 340 and 50 times, respectively, over those of the controls [4].
• These include (1) metabolic activation (to form chloroethylene oxide), (2) DNA binding of the reactive metabolite (to exocyclic etheno adducts), (3) promutagenicity of these adducts, and (4) effects of such mutations on protooncogenes/tumor suppressor genes at the gene and gene product levels [5].
• Vinyl chloride (VC), a known human and rodent carcinogen, is metabolically activated by cytochrome P450 to chloroethylene oxide (CEO), which can rearrange to chloroacetaldehyde (CAA) or undergo hydrolysis [6].
• Mutation induction in Chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2-chloroacetaldehyde [7].
• The analysis of CEO-treated calf thymus DNA samples not enriched with authentic epsilon Gua provided a precision of 15% [8].

Biological context of CHLOROETHYLENE OXIDE

• Induction of specific base-pair substitutions in E. coli trpA mutants by chloroethylene oxide, a carcinogenic vinyl chloride metabolite [9].
• In contrast to vinyl chloride, which generates chloroethylene oxide (chlorooxirane) as well as chloroacetaldehyde, this compound leads to extensive covalent protein binding of metabolites, but not to DNA binding [10].

Anatomical context of CHLOROETHYLENE OXIDE

• The applicability of the method was established by determining epsilon Gua in rats treated with CEO by portal vein injection and an unexposed human liver [8].

Associations of CHLOROETHYLENE OXIDE with other chemical compounds

• Pyrimidine nucleosides were treated with chloroethylene oxide (CEO) and 2-chloroacetaldehyde (CAA) in methanol and, following trimethylsilylation, the products were analysed by combined gas chromatography-mass spectrometry (GC-MS) [11].

Gene context of CHLOROETHYLENE OXIDE

• In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs) [12].
• recA-independent mutagenicity induced by chloroethylene oxide in E. coli [13].

Analytical, diagnostic and therapeutic context of CHLOROETHYLENE OXIDE

• In this study, we report the detection of epsilonA in the urine of rats exposed to chloroethylene oxide (CEO) using immunoaffinity columns made with specific monoclonal antibodies for enrichment, followed by quantitation by HPLC with fluorescence detection [14].
• Analysis of 1,N2-ethenoguanine and 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine in DNA treated with 2-chlorooxirane by high performance liquid chromatography/electrospray mass spectrometry and comparison of amounts to other DNA adducts [15].
• Chloracetaldehyde and chloroethylene oxide both produced similar effects on the first wave of DNA synthesis after partial hepatectomy, inhibiting the DNA synthesis rate by approx. 50% [16].
• We observed a K-ras-2 mutation pattern characteristic of chloroethylene oxide, one of the carcinogenic metabolites of VC analysed in animal models [17].

References