1. 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 : version v1Alja Štern, Špela Rozman, Bojana Žegura, 2025, complete scientific database of research data Abstract: Bisphenol AF (BPAF), Bisphenol AP (BPAP), and Bisphenol PH (BPPH) are being introduced into consumer products to replace BPA and are subsequently detected in ecosystems. This study investigates the genotoxic and endocrine-disruptive potential of these emerging bisphenols using a 3D in vitro liver spheroid model derived from Danio rerio (ZFL cell line), on the transcriptional level. The selected genes targeted DNA damage response pathways (TP53, NER, BER) and endocrine-related signalling (Table 1). ZFL spheroids were prepared by a force floating method as described by Štampar et al. (2019)1. Four-day-old ZFL spheroids were exposed to BPA (50 and 200 µM), BPAF (25 and 100 µM), BPAP (25 and 100 µM), and BPPH (10 and 50 µM) for 24 (Table 2) and 96 (Table 3) hours. Following exposure, total RNA was extracted using the RNeasy® Mini Kit (Qiagen, Germany). RNA quality and quantity were assessed prior to reverse transcription (Applied Biosystems, USA), followed by gene-specific preamplification (TATAA PreAmp GrandMasterMix, Tataa Biocenter, Sweden). Gene expression analysis was performed using TaqMan Gene Expression Assays (Applied Biosystems, USA) on the Fluidigm One 48.48 Dynamic Array IFC microfluidic system as described by Štern et al. (2024)2. The generated data was analysed using the Fluidigm Gene Expression Analysis Software and with a free-accessible web program, quantGenious3. The difference in gene expression greater than 1.5-fold was considered a biologically important up/downregulation (relative expression >1.5 or <0.66, respectively). Statistically significant differences were analysed using ANOVA and Dunnett’s multiple comparison test in GraphPad Prism v9 (GraphPad Software, San Diego, CA, USA).
Keywords: bisphenols, genotoxicity, endocrine disruption, ZFL spheroids, gene expression, data
Published in DiRROS: 30.09.2025; Views: 454; Downloads: 308
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2. Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human healthHenriqueta Louro, Ariane Vettorazzi, Adela López de Cerain, Bojana Žegura, Matjaž Novak, 2024, review article Abstract: Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.
Keywords: mycotoxin, exposure routes, genotoxicity, endocrine disruption, immunosuppression, biotransformation, toxicokinetics, tenuazonic acid, alternariol, altenuene, tentoxin, altertoxin
Published in DiRROS: 07.08.2024; Views: 1094; Downloads: 683
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