Evaluation of the effects of PFCAs on spheroid thyroid cells in primary culture: Effects on thyroid function-related genes, tumorigenesis and oxidative stress.

Perfluoroalkyl carboxylates (PFCAs) are a subgroup of Per- and Polyfluoroalkyl substances (PFAS). This study evaluated the effects of C6O4, PFOA and PFHxA on a 3D spheroid model of human thyroid cells in terms of changes in genes related to thyroid hormone functions and oxidative stress markers. Spheroids derived from normal thyroid cells (S-NHT) were exposed to PFCAs (10 ng/ml) to evaluate changes in mRNA of genes related to hormone synthesis and action, antioxidant enzymes and embryogenesis/carcinogenesis. Total ROS production was measured by using a H2DCFDA assay. Our results demonstrated that all three compounds modulated the level of the mRNA of genes associated with the synthesis and action of thyroid hormones, and they also altered thyroid homeostasis. In particular, PFHxA showed the most powerful thyroid disrupting effect. Moreover, increased mRNA expression of PAX8 and elevated ROS levels in thyroid cells suggested a potential pro-tumorigenic effect of PFCAs.