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

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.

A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice

“…Therefore in our previous study, we have investigated changes in the liver transcriptomics of mice exposed to BPA in drinking water. Data from this study suggested that BPA has a significant impact on gene expression in this organ, and may alter pathways linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma (Wiszpolska et al, 2023). About 1% of BPA does not break down and accumulates in tissues.…”

“…The experiment was carried out on twelve, 3-month-old female mice (Mus musculus, C57BL6/J/CMDB strain) with an average body weight of 30 g. The same animals were used in our previous study to investigate changes in the liver transcriptomics of mice exposed to BPA in drinking water (Wiszpolska et al, 2023). Mice were kept in the animal house (at the Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland) under constant temperature 22 °C ± 20 °C, humidity 55% ± 10% and 12:12 h light-dark cycle.…”

Plastic compounds and liver diseases: Whether bisphenol A is the only culprit

“…Potential role of BPA in inducing carcinogenicity cannot be underestimated as this endocrine disruptor is linked to causing hepatic tumours in adult mice 42 . BPA‐exposed liver transcriptome analysis points towards its association with malignant tumours 43 . Downregulation of genes like P53, BAX and P21 is reported in breast cancer cell line and liver of animal models 44 .…”

“…42 BPA-exposed liver transcriptome analysis points towards its association with malignant tumours. 43 Downregulation of genes like P53, BAX and P21 is reported in breast cancer cell line and liver of animal models. 44 Similarly, ovarian cancer was found to be aggravated in both in vitro and in vivo in experimental models through oestrogen receptor alpha (Erα) signalling.…”