Disease relevance of CCRIS 856

• Binding of the recA gene product from Escherichia coli to single-stranded polynucleotides has been investigated using poly(dA) that have been modified by chloroacetaldehyde to yield fluorescent 1,N6-ethenoadenine (epsilon A) bases [1].
• Chloroacetaldehyde reverts a new Salmonella bacterial tester strain (TA100) [2].
• The toxicity of chloroacetaldehyde is also discussed particularly in relation to the urinary bladder [3].
• Acrolein may induce hemorrhagic cystitis, whereas chloroacetaldehyde may be responsible both for nephro- and neurotoxicity [4].
• The chemical carcinogen, chloroacetaldehyde, modifies a specific site within the regulatory sequence of human cytomegalovirus major immediate early gene in vivo [5].

High impact information on CCRIS 856

• In contrast to the enzyme binding to derivatives produced by the vinyl chloride metabolite chloroacetaldehyde, the oligonucleotides up to 60-mer containing p-BQ adducts did not bind measurably to the same enzyme preparation in a gel retardation assay [6].
• Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II [7].
• However, when a single supercoiled plasmid molecule was considered, chloroacetaldehyde reacted with only one of the neighboring sequences, either 5' or 3' of the (dG-dC)16 insert, but not with both [8].
• The fluorescence intensity of DNA pretreated with chloroacetaldehyde was amplified by nearly 3-fold upon addition of the DNA helix-destabilizing protein [9].
• Reversion properties of cyclophosphamide after in vitro metabolic activation suggest that chloroacetaldehyde is not the active mutagenic form of this antineoplastic drug [2].

Chemical compound and disease context of CCRIS 856

• The intramolecular dG.dG.dC triplex structure was probed in situ for E. coli cells containing plasmid DNAs with varying lengths of poly(dG).poly(dC) tracts employing chloroacetaldehyde [10].
• Chemical modification of Escherichia coli tRNAfMet with 1 M chloroacetaldehyde, pH 5.5-6.0 at 25 degrees C, has been found to result in alteration of six cytidine and five adenosine residues in the molecule [11].
• Toxicity of ifosfamide and its metabolite chloroacetaldehyde in cultured renal tubule cells [12].
• The mutational specificity of chloroacetaldehyde (CAA), one of the metabolites of the human carcinogen vinyl chloride (VC), has been determined through the examination of Arg+ revertants in Escherichia coli AB2497 (Arg-) and identification of their tRNA suppressors [13].
• However, E. coli DERA shows low affinity to chloroacetaldehyde and is rapidly inactivated at aldehyde concentrations useful for biocatalysis [14].

Biological context of CCRIS 856

• We hypothesized that inhibition of complex I (C-I) by chloroacetaldehyde (CAA), a metabolite of IFO, is the chief cause of nephrotoxicity, and that agmatine (AGM), which we found to augment mitochondrial oxidative phosphorylation and beta-oxidation, would prevent nephrotoxicity [15].
• Our evidence suggests that 4-chlorothreonine undergoes aldol cleavage, and generation of chloroacetaldehyde at the active site of the enzyme results in inactivation [16].
• The nucleotide sequence of tRNA4Val of Drosophila melanogaster. Chloroacetaldehyde modification as an aid to RNA sequencing [17].
• New observations concerning the chloroacetaldehyde reaction with some tRNA constituents. Stable intermediates, kinetics and selectivity of the reaction [18].
• In particular, cationic effects on structure were studied by treating the supercoiled plasmid DNA harboring the chicken adult beta A globin 5' flanking sequence with an unpaired DNA base-specific probe, chloroacetaldehyde in the presence of either Mg++, Cu++, Zn++, Ca++ or Co++ ions [19].

Anatomical context of CCRIS 856

• ADO in left ventricular surface transudates and coronary effluents was rendered fluorescent with chloroacetaldehyde, and the formed ethenoadenosine derivative was quantitated with high-performance liquid chromatography fluorescence detection [20].
• In either the presence or the absence of mouse liver microsomes, 2-chloroacetaldehyde showed only feeble genetic activity, and 2-chloroethanol was completely inactive in both yeast strains [21].
• Human kidney tubules detoxify chloroacetaldehyde, a presumed nephrotoxic metabolite of ifosfamide [22].
• The effects of chloroacetaldehyde on isolated human kidney cortex tubules metabolizing lactate (a physiologic substrate in human kidneys) were investigated [22].
• Molecular mechanisms of chloroacetaldehyde-induced cytotoxicity in isolated rat hepatocytes [23].

Associations of CCRIS 856 with other chemical compounds

• The adenosine in 5- to 10-microliter samples of left ventricular epicardial surface transudates and coronary effluents was reacted with chloroacetaldehyde, and the fluorescent derivative (1,N6-ethenoadenosine) was quantitated using high pressure liquid chromatography and fluorescence detection [24].
• Formation of interstrand cross-links in chloroacetaldehyde-treated DNA demonstrated by ethidium bromide fluorescence [25].
• The helix opening was observed for all four inserts in supercoiled plasmids as a function of temperature, pH, metal ions, and buffer conditions using OsO4, diethyl pyrocarbonate, and chloroacetaldehyde probes [26].
• Human kidney tubules were demonstrated to metabolize chloroacetaldehyde at high rates, presumably via aldehyde dehydrogenase, which is very active in human kidneys [22].
• 2-Thiouridine, 4-thiouridine and the corresponding thiouracils were quantitatively modified with aqueous chloroacetaldehyde /37 degrees C, pH 3.0--6.5/. The rate-pH dependence found for the disappearance of the substrates suggested initial S-alkylation [27].

Gene context of CCRIS 856

• Modulation by acrolein and chloroacetaldehyde of multidrug resistance mediated by the multidrug resistance-associated protein (MRP) [28].
• Ifosfamide nephrotoxicity is attributed to the formation of a toxic metabolite, chloroacetaldehyde, via N-dechloroethylation, a reaction that is purportedly catalyzed by CYP3A and CYP2B6 [29].
• In contrast, Xpa(-/-) neurons were more sensitive than either wild type or Aag(-/-) neurons to CAA (>10 microM), but less sensitive than Aag(-/-) neurons to Me-Lex [30].
• Underlying this work is the hypothesis that renal ontogeny is involved in the expression and activity of the cytochrome P450 (CYP) enzymes responsible for IF metabolism to the nephrotoxic chloroacetaldehyde [31].
• The binding of the recA gene product from E. coli to double-stranded and single-stranded nucleic acids has been investigated by following the change in melting temperature of duplex DNA and the fluorescence of single-stranded DNA or poly(dA) modified by reaction with chloroacetaldehyde [32].

Analytical, diagnostic and therapeutic context of CCRIS 856

• Determination of chloroacetaldehyde in air by differential pulse polarography [33].
• The ability of the sequences to assume a stably unpaired conformation was shown by reactivity with chloroacetaldehyde which is specific for unpaired DNA bases, as well as two-dimensional gel electrophoresis of topoisomers [34].
• These assays and previously developed immunoassays for 1,N6-ethenodeoxy-adenosine (1,N6-epsilon dAdo) and 3,N4-ethenodeoxycytidine (3,N4-epsilon dCyd) were used to measure etheno adduct levels in DNA of cells exposed to chloroacetaldehyde [35].
• Detection of N2,3-ethanoguanine in DNA after treatment with chloroacetaldehyde in vitro [36].
• Southern blot analysis of resulting DNA fragments revealed that N-acetoxy-AAF detects non-B DNA structures in common with another chemical carcinogen, chloroacetaldehyde, which reacts specifically with unpaired adenine and cytosine residues [37].

References