Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 μg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.
Keywords: Bisphenol S; Imaging mass spectrometry; In situ imaging of protein and lipid; Tumor proliferation.
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