Journal
TOXICOLOGY MECHANISMS AND METHODS
Volume 23, Issue 6, Pages 389-395Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/15376516.2012.762570
Keywords
Arsenic; immuno-spin trapping; reactive oxygen species
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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 (GSH) 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 mu M), stimulated ODD only at levels above the LC50 of a 48 h exposure (17 mu M). 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 mu M) caused ODD at levels below the LC50 of a 48 h exposure (1.5 mu M), which were greatly increased by GSH 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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