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Abstract
Perchlorate (ClO4 −), which is a ubiquitous and persistent ion, competitively interferes with iodide (I) accumulation in the thyroid, producing I deficiency (ID), which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that ClO4 − presents little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of ID adults and mothers require extra consideration. In an attempt to determine whether the effects on gene expression were similar, the thyroidal effects of ClO4 − (10 mg/kg) treatment for 14 d in drinking water were compared with those produced by 8 wk of ID in rats. The thyroids were collected (n = 3 each group) and total mRNA was analyzed using the Affymetrix Rat Genome 230 2.0 GeneChip. Changes in gene expression were compared with appropriate control groups. The twofold gene changes due to ID were compared with alterations due to ClO4 − treatment. One hundred and eighty-nine transcripts were changed by the ID diet and 722 transcripts were altered by the ClO4 − treatment. Thirty-four percent of the transcripts changed by the I-deficient diet were also altered by ClO4 − and generally in the same direction. Three specific transporter genes, AQP1, NIS, and SLC22A3, were changed by both treatments, indicating that the membrane-specific changes were similar. Iodide deficiency primarily produced alterations in retinol and calcium signaling pathways and ClO4 − primarily produced changes related to the accumulation of extracellular matrix proteins. This study provides evidence that ClO4 −, at least at this dose level, changes more genes and alters different genes compared to ID.
Acknowledgments
Supported by U.S. EPA STAR cooperative agreement R832134. We thank Drs. Keys and Li for statistical support and the UGA diagnostic laboratory for TSH analysis. This material was also presented as a poster at the 2010 Society of Toxicology meeting: J. N. McDougal, K. L. Jones, B. Fatuyi, and J. W. Fisher. Gene expression in thyroid after perchlorate treatment compared to iodine deficiency. #2094. The Toxicologist CD—An Official Journal of the Society of Toxicology, volume 109, number 1, March 2010.