20.500.12556/DiRROS-23737 Exploring the genotoxic potential of Bisphenol A and its emerging alternatives in an advanced in vitro 3D zebrafish hepatic cell model 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. BPA BPAF BPAP BPPH cytotoxicity genotoxicity ZFL spheroids citotoksičnost genotoksičnost ZFL sferoidi true false true Angleški jezik Slovenski jezik Neznano 2025-09-26 14:23:50 2025-09-26 14:23:50 2025-10-24 03:54:56 0000-00-00 00:00:00 2025 0 0 Soavtorji: Katja Kološa, Špela Rozman, Bojana Žegura; Nasl. z nasl. zaslona; Opis vira z dne 26. 9. 2025; str. 1-12 Vol. 1001, [article no.] 180527 Oct. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2025-10-25 615.9 1879-1026 10.1016/j.scitotenv.2025.180527 250674691 https://doi.org/10.1016/j.scitotenv.2025.180527 1 ac03bd77-9ad3-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35177 RAZ_Stern_Alja_2025.pdf RAZ_Stern_Alja_2025.pdf 1 94B7E676551DA78EF55B3655643B7DD5 a13d79595cc61c0516484de810306e507e4ed8132dffdfb681722e91f29ccd90 c0728bc0-9ad3-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35178 Nacionalni inštitut za biologijo Deregulations of DNA damage-responsive genes, genes involved in the endocrine system, in an advanced in vitro 3D zebrafish hepatic cell model after exposure to Bisphenol A (BPA) and its emerging alternatives BPAF, BPAP and BPPH 0 0 0