Differential Effects of Bisphenol A on Thyroid Cell Viability, Proliferation, and Migration Are Influenced by Genetic Background

Bisphenol A (BPA) is a common endocrine disruptor that poses a public health risk owing to its potential effects on thyroid function. However, its role in thyroid cancer development is unclear. This study investigated BPA's genotype-dependent effects of BPA on cellular processes in human thyroid cell lines. We exposed a non-tumorigenic cell line (Nthy-ori 3 − 1) and two papillary thyroid carcinoma cell lines, BCPAP (BRAF V600E) and TPC-1 (RET/PTC), to BPA concentrations (0.1–1.0 µg/mL) and assessed their viability, proliferation, and migration. The results indicate that BPA induces distinct, genotype-dependent responses. At higher concentrations (0.8-1.0 µg/mL), non-tumorigenic cells exhibited significant dose-dependent cytotoxicity but paradoxically showed enhanced migration compared to untreated cells. In cancer cell lines, TPC-1 cells exhibited relative resistance to BPA with no significant changes in migration, whereas BCPAP cells showed reduced proliferation and significant impairment of wound closure. Our findings demonstrate that BPA exerts dual and opposing effects on thyroid cells, depending on the genetic background. Genotype-specific susceptibilities, cytotoxic and pro-migratory responses in normal cells, and a clear anti-migratory effect restricted to BRAF-mutant cells underscore the complex role of BPA in thyroid pathophysiology. These results suggest that genetic background is a critical determinant of cellular susceptibility to endocrine disruptors.