Genetic Background Dictates the Dichotomous Effects of Bisphenol A on Thyroid Cell Viability, Proliferation, and Migration

Bisphenol A (BPA), a common endocrine disruptor, poses a public health risk due to its potential effects on thyroid function. However, its role in thyroid cancer development remains unclear. This study investigated BPA's genotype-dependent effects on cellular processes in human thyroid cell lines. We exposed a non-tumorigenic thyroid cell line (Nthy-ori 3-1) and two papillary thyroid carcinoma cell lines, BCPAP (BRAF V600E) and TPC-1 (RET/PTC rearrangement), to BPA concentrations (0.1–1.0 µg/mL). Subse-quently, cellular viability, proliferation, and migration were assessed. BPA induced distinct genotype-dependent responses. At higher concentrations (0.8-1.0 µg/mL), non-tumorigenic cells exhibited significant dose-dependent cytotoxicity but paradoxi-cally showed enhanced migration. In the cancerous cell lines, TPC-1 cells did not ex-hibit inhibition of proliferation or changes in migration, while BCPAP cells were rela-tively resistant to cytotoxicity but showed reduced proliferation and significantly im-paired migration. Our findings demonstrate that BPA exerts dual and opposing effects on thyroid cells, depending on the genetic background. These genotype-specific sus-ceptibilities, cytotoxic and pro-migratory effects in normal cells, and in RET/PTC-positive cells, and antimigratory effects in BRAF-mutant cells underscore the complex role of BPA in thyroid pathophysiology. These results demonstrate that ge-netic background is a critical determinant of cellular susceptibility, suggesting that BPA exposure may differentially influence thyroid cancer initiation and progression.