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Julie A. Gosse, Vivien F. Taylor, Brian P. Jackson, Joshua W. Hamilton and Jack E. Bodwell Monomethylated trivalent arsenic species disrupt steroid receptor interactions with their DNA response elements at non-cytotoxic cellular concentrations Journal of Applied Toxicology 34

Version of Record online: 14 JUN 2013 | DOI: 10.1002/jat.2898

Steroid receptor (SR) driven gene expression in cells is inhibited by inorganic arsenite (iAs+3). Fluorescence polarization experiments show that neither iAs+3 nor dimethylated (DMA+3) arsenite affect glucocorticoid (GR) and progesterone receptor (PR) interactions with DNA response elements (GREs). However, monomethylated arsenic strongly inhibits GR-GRE and PR-GRE binding. The concentration of monomethylated arsenite in iAs+3-treated hepatoma cells is sufficient to inhibit SR-GRE interactions. Thus, arsenic's endocrine disruption may be caused by methylated metabolites' disruption of SR binding to DNA response elements.

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