Bisphenol A is more potent than bisphenol S in influencing the physiological and pathological functions of lungs via inducing lung fibrosis and stimulating metastasis

Bisphenol A (BPA) is widely used in the production of plastics, food containers, and receipt ink globally. However, research has identified it as an endocrine disruptor, affecting the hormonal balance in living organisms. Bisphenol S (BPS), one of the alternative substances, was developed, but its effects on human health and the underlying mechanisms remain unclarified. Specifically, research on the effects of oral exposure to bisphenol on the lungs is lacking. We examined the potential differences in toxicity between these compounds in lung cells in vitro and in vivo. Our toxicity mechanism studies on MRC5 and A549 cells exposed to BPA or BPS revealed that BPA induced actin filament abnormalities and activated epithelial–mesenchymal transition (EMT). This finding suggests an increased potential for lung fibrosis and metastasis in lung cancer. However, given that BPS was not detected at the administered dose and under the specific experimental conditions, the probability of these occurrences is considered minimal. Additionally, animal experiments confirmed that oral exposure to BPA activates EMT in the lungs. Our study provides evidence that prolonged oral exposure to BPA can lead to EMT activation in lung tissue, similar to that observed in cell experiments, suggesting the potential to induce lung fibrosis. This research emphasizes the importance of regulating the use of BPA to mitigate its associated pulmonary toxicity. Furthermore, it is significant that within the parameters of our experimental conditions, BPS did not exhibit the toxicological pathways clearly evident in BPA. [Display omitted] •BPA and BPS have varying cytotoxic patterns in lung-derived cells.•BPA exposure induces the formation of disconnected actin filaments in lung organed cells.•BPA treatment leads to upregulation of fibronectin expression, a key indicator of lung fibrosis in vitro and in vivo.•BPA makes lung cancer cells move more through the EMT pathway by reducing E-cadherin expression, while BPS doesn't have this effect.