| Oxidative DNA Damage After Acute Exposure to Arsenite and Monomethylarsonous Acid in Biomethylation-Deficient Human Cells. | |
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MedLine Citation:
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PMID: 23301828 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Abstract The carcinogen inorganic arsenic (iAs) undergoes biomethylation (BMT) in some cells. The methylated metabolite, monomethylarsonous (MMA(3+)), may cause oxidative DNA damage (ODD). With chronic iAs exposure, BMT-competent cells show ODD while BMT-deficient do not. To further define these events, we studied ODD produced by acute iAs or MMA(3+) in the BMT-deficient human prostate cell line, RWPE-1. ODD, measured by the immuno-spin trapping method, was assessed after exposure to iAs or MMA(3+) alone, with the arsenic BMT inhibitor selenite or after glutathione depletion. The expression of oxidative stress related genes (HO-1, SOD-1, SOD-2, Nrf2 and Keap-1) was also assessed. Exposure to iAs at 24 h (0-20 µM), stimulated ODD only at levels above the LC(50) of a 48 h exposure (17 µM). If iAs induced ODD it also activated oxidative stress-related genes. Selenium did not alter iAs-induced ODD. MMA(3+) at 24 h (0-0.5 µM) caused ODD at levels below the LC(50) of a 48 h exposure (1.5 µM), which were greatly increased by glutathione depletion but not selenite. MMA(3+) induced ODD at levels not activating oxidant stress response genes. Overall, iAs induced ODD in BMT deficient cells only at toxic levels. MMA(3+) caused ODD at non-toxic levels, independently of cellular BMT capacity and in a fashion not requiring further BMT. |
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Authors:
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Ruben Orihuela; Chikara Kojima; Erik J Tokar; Rachel J Person; Yuanyuan Xu; Wei Qu; Michael P Waalkes |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-10 |
Journal Detail:
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Title: Toxicology mechanisms and methods Volume: - ISSN: 1537-6524 ISO Abbreviation: Toxicol. Mech. Methods Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101134521 Medline TA: Toxicol Mech Methods Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Inorganic Toxicology Group, National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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