Bisphenol A (BPA) is an environmental toxin widely used in the production of polycarbonate plastics. A correlation exists between BPA tissue contamination and the occurrence of pathological conditions, including cancer. First-passage detoxification of high BPA amounts in the liver promotes hepatotoxicity and morphological alterations of this organ, but there is a lack of knowledge about the molecular mechanisms underlying these phenomena. This prompted us to investigate changes in the liver transcriptomics of 3-month-old female mice exposed to BPA (50 mg/kg) in drinking water for 3 months. Five female mice served as controls. The animals were euthanized, the livers were collected, and RNA was extracted to perform RNA-seq analysis. The multistep transcriptomic bioinformatics revealed 120 differentially expressed genes (DEGs) in the BPA-exposed samples. Gene Ontology (GO) annotations indicated that DEGs have been assigned to many biological processes, including “macromolecule modification” and “protein metabolic process”. Several of the revealed DEGs have been linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma. Data from this study suggest that BPA has a significant impact on gene expression in the liver, which is predictive of the carcinogenic potential of this compound in this organ.
双酚A（BPA）是一种广泛应用于聚碳酸酯塑料生产的环境毒素。BPA组织污染与包括癌症在内的多种病理状态存在相关性。肝脏对高剂量BPA的首过解毒作用会引发肝毒性及肝脏形态学改变，但关于这些现象背后的分子机制尚缺乏深入研究。为此，我们通过饮用水对3月龄雌性小鼠进行为期3个月的BPA暴露（50 mg/kg），并对其肝脏转录组学变化展开研究。实验设置5只雌性小鼠作为对照组。实验结束后对动物实施安乐死，采集肝脏组织并提取RNA进行RNA-seq分析。多步骤转录组生物信息学分析显示，BPA暴露样本中存在120个差异表达基因（DEGs）。基因本体（GO）注释表明这些差异表达基因参与多种生物过程，包括"大分子修饰"和"蛋白质代谢过程"。部分发现的差异表达基因与严重代谢性肝病及恶性肿瘤（特别是肝细胞癌）的发病机制相关。本研究数据表明，BPA对肝脏基因表达具有显著影响，这预示着该化合物在该器官中具有致癌潜力。
The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies
肿瘤(癌症)患者之家