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Oxidative DNA Damage After Acute Exposure to Arsenite and Monomethylarsonous Acid in Biomethylation-Deficient Human Cells.
MedLine Citation:
PMID:  23301828     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Ruben Orihuela; Chikara Kojima; Erik J Tokar; Rachel J Person; Yuanyuan Xu; Wei Qu; Michael P Waalkes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-10
Journal Detail:
Title:  Toxicology mechanisms and methods     Volume:  -     ISSN:  1537-6524     ISO Abbreviation:  Toxicol. Mech. Methods     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101134521     Medline TA:  Toxicol Mech Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
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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