Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method originally developed to detect topoisomerase DNA complexes has been adapted to determine DNA-protein cross-links formed in cells following their exposure in vitro and in vivo to cross-linking agents. A preliminary study on welders and controls has been carried out to assess the feasibility of this assay to detect human exposure to chromium (Cr) and nickel (Ni) that are associated with increased DNA-protein cross-links. The percentage of cross-link was significantly higher among welders (1.85% +/- 1.14) than among controls (1.17% +/- 0.46; p = .01) Cross-links were not affected by age, weight, or smoking status. The assay developed has substantial advantages over previous methods, being considerably more simple, inexpensive, and sensitive.
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PMID:Preliminary report on a simple new assay for DNA-protein cross-links as a biomarker of exposures experienced by welders. 823 Feb 97

Several studies have shown that hexavalent chromium [Cr(VI)] induces apoptosis in a variety of in vitro test systems. We instilled intra-tracheally either saline or sodium dichromate (0.25 mg/kg body weight), for three consecutive days, to Sprague-Dawley rats. TUNEL analyses showed a marked increase of the apoptotic index in both bronchial epithelium and lung parenchyma of Cr(VI)-treated rats, but no effect was detected in their liver. In parallel, the expression of 13 out of 18 apoptosis-related genes, evaluated by cDNA array analysis, was significantly enhanced in rat lung. The overexpressed genes included c-Jun N-terminal kinases 1, 2 and 3, bcl-x, bcl-2-associated death promoter and bcl-2-related ovarian killer protein, caspases 1, 3 and 6, DNase I precursor, DNA topoisomerases I and II alpha, and poly(ADP-ribose) polymerase. The enhancement of p53 expression in the lung was borderline to statistical significance. Expressions of bcl-2, bax-alpha, mdm2 and DNA topoisomerase IIB were not enhanced to a significant extent in lung. No induction of gene expression was observed in rat liver. RT-PCR analyses confirmed that Cr(VI) enhances the expression of c-Jun N-terminal kinase 1, caspase 6, and DNase I precursor but not that of bcl-2 in lung, while none of these genes was overexpressed in the liver of Cr(VI)-treated rats. The lack of stimulation of apoptosis in the liver parallels the failure of Cr(VI) to produce genotoxic damage, as we previously observed under identical experimental conditions. These negative findings may be ascribed to reduction of Cr(VI) to Cr(III) when traveling from the respiratory tract to the liver. On the other hand, induction of apoptosis in the respiratory tract parallels the occurrence of genotoxic effects and oxidative DNA damage produced by Cr(VI) in the same tissue. As previously shown in another laboratory, Cr(VI) did not induce lung tumors after 30 months of administration of the same daily dose. Therefore, apoptosis is likely to provide a protective mechanism at a post-genotoxic stage of Cr(VI) carcinogenesis.
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PMID:Induction of apoptosis in the lung but not in the liver of rats receiving intra-tracheal instillations of chromium(VI). 1196 Sep 10

Trivalent chromium is a metal required for proper sugar and fat metabolism. However, it has been suggested that it causes DNA damage in in vitro test systems, although in vivo toxicity has not yet been proved. In the present study, the effect of Cr3+ on bacterial cells was tested with the Pro-Tox (C) assay, and its cellular uptake was measured with flame atomic absorption spectroscopy. The potential genotoxicity of Cr3+ was further examined by the study of its influence on a bacterial type II topoisomerase. Cr3+ was shown to cause DNA damage and inhibit topoisomerase DNA relaxation activity, probably by preventing the formation of the covalent link between enzyme and double helix. In addition, Cr3+ decreases the viability and/or proliferation rate of eukaryotic cells such as murine B16 melanoma cells and human MCF-10A neoT ras-transformed human epithelial cells. The possible implication for Cr3+ intake by humans is discussed.
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PMID:Genotoxicity of trivalent chromium in bacterial cells. Possible effects on DNA topology. 1211 5