Work

Exploring the genotoxic potential of Bisphenol A and its emerging alternatives in an advanced in vitro 3D zebrafish hepatic cell model

Year: 2025

Type: article

Abstract: With global restrictions on Bisphenol A (BPA), various BPA alternatives are increasingly found in ecosystems, raising concerns. This study focuses on the genotoxic potential of three emerging BPA alternatives — Bisphenol AF (BPAF), Bisphenol AP (BPAP), and Bisphenol PH (BPPH) — using an advanced in vitro 3D model system, spheroids, prepared from a Zebrafish ( Danio rerio ) liver cell line (ZFL). Their cytotoxicity was evaluated using the CellTiter-Glo® 2.0 assay, while their genotoxic potential was assessed using the comet assay, γH2AX assay, and toxicogenomic analysis. The BPA alternatives were more cytotoxic to ZFL spheroids than BPA. Non-cytotoxic concentrations caused transient DNA damage without a significant increase in DNA double-strand breaks (DSBs). The toxicogenomic analysis confirmed these findings, indicating activation of the TP53 DNA damage response pathway, the nucleotide excision repair (NER) and base excision repair (BER) mechanisms, likely in response to bulky DNA lesions and oxidative DNA damage. In addition, the gene expression analysis indicated the influence of the tested BPs on the endocrine system. Our results indicate that BPAF, BPAP and BPPH have considerable genotoxic potential and pose a significant ecotoxicological risk, underscoring the need for further investigation and careful consideration of these chemicals as BPA replacements. • Zebrafish liver cell (ZFL) spheroids are a sensitive in vitro model for testing BPs. • BPAF, BPAP, and BPPH showed higher cytotoxicity in ZFL spheroids than BPA. • The tested BPs caused transient DNA damage but no DNA double-strand breaks. • Toxicogenomics indicated induction of the TP53 pathway and NER/BER repair mechanisms. • The deregulation hormone receptor genes indicated significant endocrine-disruptive potential.

Source: The Science of The Total Environment

DOI: 10.1016/j.scitotenv.2025.180527

Authors: Alja Štern, Katja Kološa, Špela Rozman, Bojana Žegura

Institutions: University of Ljubljana, National Institute of Biology

Language: English

Topic: Carcinogens and Genotoxicity Assessment

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,250