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基于转录组学研究的双酚A在肝脏中的致癌潜力

The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies.

作者信息

Wiszpolska Marta, Lepiarczyk Ewa, Maździarz Mateusz A, Paukszto Łukasz, Makowczenko Karol G, Lipka Aleksandra, Łopieńska-Biernat Elżbieta, Makowska Krystyna, Gonkowski Sławomir, Correia-de-Sá Paulo, Majewska Marta

机构信息

Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland.

Department of Botany and Nature Protection, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-727 Olsztyn, Poland.

出版信息

Cancers (Basel). 2023 Oct 17;15(20):5014. doi: 10.3390/cancers15205014.

Abstract

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.

摘要

双酚A(BPA)是一种广泛用于生产聚碳酸酯塑料的环境毒素。BPA组织污染与包括癌症在内的病理状况的发生之间存在关联。肝脏中高含量BPA的首过解毒会促进肝毒性以及该器官的形态改变,但对于这些现象背后的分子机制尚缺乏了解。这促使我们研究3个月大的雌性小鼠饮用含BPA(50毫克/千克)的水3个月后肝脏转录组学的变化。五只雌性小鼠作为对照。将动物安乐死,收集肝脏,并提取RNA以进行RNA测序分析。多步骤转录组生物信息学揭示了BPA暴露样本中有120个差异表达基因(DEG)。基因本体论(GO)注释表明,DEG已被归入许多生物过程,包括“大分子修饰”和“蛋白质代谢过程”。一些已揭示的DEG与严重代谢性肝病和恶性肿瘤(特别是肝细胞癌)的发病机制有关。这项研究的数据表明,BPA对肝脏中的基因表达有重大影响,这预示着该化合物在该器官中的致癌潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce07/10605469/dc26dc9d5992/cancers-15-05014-g001.jpg

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