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

Author:

Wiszpolska Marta1ORCID,Lepiarczyk Ewa1ORCID,Maździarz Mateusz A.2,Paukszto Łukasz2ORCID,Makowczenko Karol G.3ORCID,Lipka Aleksandra4ORCID,Łopieńska-Biernat Elżbieta5ORCID,Makowska Krystyna6ORCID,Gonkowski Sławomir7ORCID,Correia-de-Sá Paulo8ORCID,Majewska Marta1ORCID

Affiliation:

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

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

3. Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, Poland

4. Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway

5. Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland

6. Department of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-957 Olsztyn, Poland

7. Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-957 Olsztyn, Poland

8. Laboratório de Farmacologia e Neurobiologia, Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal

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.

Funder

School of Medicine, Collegium Medicum

University of Warmia and Mazury in Olsztyn and National Science Centre in Poland

Portuguese Foundation for Science and Technology

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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