| Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. | |
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MedLine Citation:
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PMID: 11172004 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although arsenic is a well-established human carcinogen, the mechanisms by which it induces cancer remain poorly understood. We previously showed arsenite to be a potent mutagen in human-hamster hybrid (A(L)) cells, and that it induces predominantly multilocus deletions. We show here by confocal scanning microscopy with the fluorescent probe 5',6'-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate that arsenite induces, within 5 min after treatment, a dose-dependent increase of up to 3-fold in intracellular oxyradical production. Concurrent treatment of cells with arsenite and the radical scavenger DMSO reduced the fluorescent intensity to control levels. ESR spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-1-hydroxypiperidine (TEMPOL-H) as a probe in conjunction with superoxide dismutase and catalase to quench superoxide anions and hydrogen peroxide, respectively, indicates that arsenite increases the levels of superoxide-driven hydroxyl radicals in these cells. Furthermore, reducing the intracellular levels of nonprotein sulfhydryls (mainly glutathione) in A(L) cells with buthionine S-R-sulfoximine increases the mutagenic potential of arsenite by more than 5-fold. The data are consistent with our previous results with the radical scavenger DMSO, which reduced the mutagenicity of arsenic in these cells, and provide convincing evidence that reactive oxygen species, particularly hydroxyl radicals, play an important causal role in the genotoxicity of arsenical compounds in mammalian cells. |
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Authors:
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S X Liu; M Athar; I Lippai; C Waldren; T K Hei |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2001-02-06 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 98 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-02-26 Completed Date: 2001-04-19 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 1643-8 Citation Subset: IM; S |
Affiliation:
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Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arsenites / pharmacology* Buthionine Sulfoximine / pharmacology Carcinogens / pharmacology* Cricetinae Humans Hydroxyl Radical / metabolism* Mutagens / pharmacology* Piperidines / pharmacology Reactive Oxygen Species / metabolism* Sodium Compounds / pharmacology* Spin Trapping / methods |
| Grant Support | |
ID/Acronym/Agency:
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ES 01900/ES/NIEHS NIH HHS; GM 40168/GM/NIGMS NIH HHS; P42 ES 10349/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arsenites; 0/Carcinogens; 0/Mutagens; 0/Piperidines; 0/Reactive Oxygen Species; 0/Sodium Compounds; 13768-07-5/sodium arsenite; 15502-74-6/arsenite; 2403-88-5/lastar A; 3352-57-6/Hydroxyl Radical; 5072-26-4/Buthionine Sulfoximine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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