Identification of Classifiers for Increase or Decrease of Thyroid Peroxidase Activity in the FTC-238/hTPO Recombinant Cell Line

Abstract

Thyroid peroxidase (TPO) plays an important role in thyroid hormone biosynthesis, as it catalyzes all of the essential steps in iodide organification. TPO activity can be detected using the guaiacol assay; however, this assay is complex and very time-consuming. Therefore, we focused on devising a simplified method using microarrays to detect changes in TPO activity, which is a target for disruption of the thyroid hormone axis. These experiments have systematically assessed the potential utility of transcriptomic end points as enhancements to the guaiacol assay. Previously, we demonstrated that benzophenone-2, benzophenone, perfluorooctane sulfonate, bisphenol A bis ether, and vinclozolin decreased TPO activity, and that dibutyl phthalate, carbaryl, dibenzo(a,h)anthracene, benzo(a)pyrene, and methylmercury increased TPO activity. In this work, we used human oligonucleotide chips to examine changes in the gene expression profile of FTC-238 human follicular thyroid carcinoma cells expressing human recombinant TPO, after exposure of the cells to TPO activity-disrupting agents. We identified 362 classifiers that could predict the effect of the toxicants on TPO activity with about 70% accuracy. These classifiers are potential markers for predicting the effects of chemicals on thyroid hormone production.