Bisphenol A Induces DNA Damage and Differential Cytotoxicity in Thyroid Cells: High-Dose Effects Challenge Regulatory...

Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been implicated in carcinogenesis; however, its effects on thyroid cells remain unclear. This study investigated BPA-induced cytotoxicity and genotoxicity in thyroid cell lines, including normal follicular (Nthy-ori 3-1), papillary carcinoma (TPC-1 and BCPAP) and anaplastic carcinoma (8505C) cells, including exposure to the specific migration limit (SML) established by Brazilian regulations (1 μg/mL). Cells were exposed for 24 and 48 h, and membrane integrity, metabolic activity, and DNA damage were assessed using trypan blue exclusion, CCK-8, and comet assays, respectively. Nthy-ori 3-1 exhibited non-monotonic cytotoxicity, with 60% mortality at the SML (24 h). The 8505C line displayed notable resistance to membrane damage at high concentrations but was highly sensitive to genotoxicity, which intensified after BPA exposure and may be related to TP53 mutations. The SML dose caused significant DNA damage in normal cells, whereas papillary lines were less affected. These findings demonstrate cell-context-dependent BPA effects and suggest that current regulatory thresholds may not adequately protect thyroid health, particularly in individuals with pre-existing thyroid conditions. BPA's impact involves both metabolic disruption and impaired DNA repair pathways, supporting its potential carcinogenicity.