Toxins最新文献

{"title":"An Unusual Outbreak of Ochratoxicosis Associated with <i>Trigonella foenum-graecum</i> Ingestion in Ruminants from Different Farms of Sicily.","authors":"Maria Rizzo, Patrizia Licata, Pietro Paolo Niutta, Michela Pugliese, Vito Macaluso, Giovanna Lucrezia Costa, Giuseppe Bruschetta, Fabio Bruno","doi":"10.3390/toxins17030120","DOIUrl":"10.3390/toxins17030120","url":null,"abstract":"<p><p><i>Trigonella foenum-graecum</i> is a widely cultivated legume in Mediterranean regions, and it is used for human and animal consumption, as well as for medical purposes. High temperatures and abundant rainfall during the spring season in Sicily favor the formation of an environment suitable for the growth and proliferation of fungi with the production of mycotoxins. In this study, ochratoxin A, aflatoxin, deoxynivalenol, zearalenone, fumonisin, and T-2 toxin concentrations in <i>Trigonella foenum-graecum</i> were determined in feed administered to ruminants and also in blood samples from cattle and sheep in order to evaluate the toxicity correlated to the possible presence of these mycotoxins based on the clinical signs observed in the animals. Analyses of mycotoxins in fenugreek and blood samples were conducted using the enzyme immunoassay KIT. Five extensive farms sited in the northwest of the Sicily region, with a total of 90 intoxicated animals, reported a concomitant unusual outbreak of neurological disorders. Decreased spinal reflex responses, postural abnormalities associated with weakness or recumbency, and hyperesthesia of the limbs suggested a problem regarding the peripheral nervous system. The mortality rate recorded was very high, even reaching 100% of the intoxicated animals. OTA intoxication in Sicilian ruminants represents an important warning on the vulnerability of farms to mycotoxin contamination and underlines the importance of preventive measures and monitoring in animal health management.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cylindracin, a Fruiting Body-Specific Protein of <i>Cyclocybe cylindracea</i>, Represses the Egg-Laying and Development of <i>Caenorhabditis elegans</i> and <i>Drosophila melanogaster</i>.","authors":"Yamato Kuratani, Akira Matsumoto, Ayako Shigenaga, Koji Miyahara, Keisuke Ekino, Noriaki Saigusa, Hiroto Ohta, Makoto Iwata, Shoji Ando","doi":"10.3390/toxins17030118","DOIUrl":"10.3390/toxins17030118","url":null,"abstract":"<p><p>Mushrooms are a valuable source of bioactive compounds to develop efficient, secure medicines and environmentally friendly agrochemicals. Cylindracin is a small cysteine-rich protein that is specifically expressed in the immature fruiting body of the edible mushroom <i>Cyclocybe cylindracea</i>. Recombinant protein (rCYL), comprising the C-terminal cysteine-rich domain of cylindracin, inhibits the hyphal growth and conidiogenesis of filamentous fungi. Here, we show that rCYL represses the egg-laying and development of <i>Caenorhabditis elegans</i> and <i>Drosophila melanogaster</i>. The feeding of rCYL at 16 µM reduced the body volume of <i>C. elegans</i> larvae to approximately 60% when compared to the control. At the same concentration, rCYL repressed the frequencies of pupation and emergence of <i>D. melanogaster</i> to 74% and 40%, respectively, when compared to the control. In virgin adult flies, feeding of rCYL at 47 µM substantially repressed the frequency of egg-laying, and the pupation and emergence of the next generation, especially for females. These inhibitory effects of rCYL gradually disappeared after ceasing the ingestion of rCYL. The use of fluorescence-labeled rCYL revealed that the protein accumulates specifically at the pharynx cuticles of <i>C. elegans</i>. In <i>D. melanogaster</i>, fluorescence-labeled rCYL was detected primarily in the midguts and to a lesser degree in the hindguts, ovaries, testes, and malpighian tubules. rCYL was stable against trypsin, chymotrypsin, and pepsin, whereas it did not inhibit proteolytic and glycolytic enzymes in vitro. rCYL oligomerized and formed amyloid-like aggregates through the binding to heparin and heparan sulfate in vitro. These results suggest that rCYL has potential as a new biocontrol agent against pests.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Deaths Related to Oleander Poisoning: A Review of the Literature.","authors":"Matteo Antonio Sacco, Saverio Gualtieri, Aurora Princi, Alessandro Pasquale Tarallo, Maria Cristina Verrina, Lucia Tarda, Luca Calanna, Santo Gratteri, Isabella Aquila","doi":"10.3390/toxins17030115","DOIUrl":"10.3390/toxins17030115","url":null,"abstract":"<p><p>Oleander poisoning, resulting from the ingestion of Nerium oleander or Thevetia peruviana, is a serious toxicological issue in various parts of the world, particularly in regions where these plants grow abundantly and are easily accessible. Oleander contains potent cardiac glycosides, such as oleandrin and thevetin, which exert powerful effects on the cardiovascular system, leading to symptoms ranging from nausea and abdominal pain to severe arrhythmias and sudden cardiac death. This review summarizes the existing literature on the epidemiology, clinical features, pathophysiology, and challenges in treatment management associated with oleander poisoning. While supportive care, gastric decontamination, and the administration of digoxin-specific Fab antibody fragments (Digifab) are essential therapeutic measures, limited access to Digifab, delays in intervention, and insufficient supportive care practices remain significant complicating factors. Particular attention is given to findings from autopsy reports, which provide critical insights into the pathophysiological effects of oleander toxins and help bridge gaps in understanding fatal cases. This review acknowledges key limitations, particularly the scarcity of English-language publications, which restricts input from regions such as southern Asia and the Mediterranean-areas where oleander-related poisoning, especially in cases of intentional self-harm, is more prevalent. Additionally, this review highlights the socio-cultural dimensions of oleander ingestion, often linked to intentional self-poisoning, and emphasizes the need for enhanced preventive measures and public education. Future research efforts should prioritize addressing these gaps through autopsy-based studies and the development of more accessible and effective antidotes, which are essential to mitigate the global health burden of oleander-related mortality.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Mycotoxin Contamination of Aquaculture Feed: A Global Survey.","authors":"Christiane Gruber-Dorninger, Anneliese Müller, Roy Rosen","doi":"10.3390/toxins17030116","DOIUrl":"10.3390/toxins17030116","url":null,"abstract":"<p><p>Plant-based materials are increasingly being used as ingredients of aquaculture feed. These materials are prone to mycotoxin contamination, as mycotoxigenic fungi infest crop plants in the field and agricultural products during storage. As mycotoxins can cause toxic effects in aquatic animals, their occurrence in feedstuffs should be monitored. To this end, we performed an extensive global survey of mycotoxin contamination in aquaculture feed and plant-based feed raw materials. We collected samples of compound feed for fish (n = 226) and shrimps (n = 61), maize (n = 3448), maize DDGS (n = 149), wheat (n = 1578), soybean (n = 428), and rice (n = 65). We analyzed concentrations of 51 mycotoxins, emerging mycotoxins, masked mycotoxins, and mycotoxin metabolites. Mycotoxins were almost ubiquitously present in compound feed, as >90% of samples were contaminated with at least one mycotoxin. Feed raw materials exhibited distinct mycotoxin occurrence patterns consistent with known susceptibility to fungal pathogens and with their production process. Unsafe concentrations of aflatoxin B₁ exceeding the EU maximum level were detected in 7.2% of fish feed samples. While most feedstuffs complied with EU guidance values for deoxynivalenol, zearalenone, and fumonisins, a comparison of detected concentrations with dietary concentrations reported to cause adverse effects in fish and shrimps in published studies indicated that significant fractions of samples contained potentially harmful levels of these mycotoxins. In addition to regulated mycotoxins, several emerging mycotoxins (e.g., enniatins, beauvericin, alternariol, moniliformin) were prevalent. Feed was frequently co-contaminated with multiple mycotoxins indicating a risk of combined effects. In conclusion, mycotoxin contamination was common in aquaculture feed and fractions of samples were contaminated with mycotoxin levels known to exert adverse effects in aquaculture species. Results of this survey highlight the necessity for targeted studies on the effects of frequently detected mycotoxin mixtures and emerging mycotoxins in fish and shrimp.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain Reduction with Repeated Injections of Botulinum Toxin A in Upper Limb Spasticity: A Longitudinal Analysis from the ULIS-III Study.","authors":"Lynne Turner-Stokes, Khan Buchwald, Stephen A Ashford, Klemens Fheodoroff, Jorge Jacinto, Ajit Narayanan, Richard J Siegert","doi":"10.3390/toxins17030117","DOIUrl":"10.3390/toxins17030117","url":null,"abstract":"<p><p>Pain reduction is a common goal of the treatment of upper limb spasticity with botulinum toxin (BoNT-A). ULIS-III was a large international, observational, longitudinal study (N = 953) conducted in real-life clinical practice over two years. In this secondary post hoc analysis, we examine whether goals for pain reduction were met over repeated injection cycles. We report serial changes in pain severity and explore predictors of pain reduction and injection frequency. Patients were selected if pain reduction was a primary/secondary goal for at least one cycle (n = 438/953). They were assessed at the start and end of each cycle using the goal attainment T-score alongside a self-report of pain severity (range 0-10). Across all cycles, pain-related goals were set for 1189/1838 injections (64.7%) and were achieved in 839 (70.6%). Patients continued to show a significant reduction in pain (<i>p</i> < 0.001) for each injection up to seven cycles, with some cumulative benefit (<i>p</i> < 0.001). Those requiring more frequent injections tended to have higher starting pain scores and a smaller reduction in pain score, but these differences were not significant when other covariates (age, previous injection history, time since onset, severity and distribution of spasticity) were taken into account (<i>p</i> > 0.713). Conclusion: Repeated BoNT-A administration continued to result in a significant reduction in upper limb spasticity-related pain, regardless of patient-related factors.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short Peptides from Asian Scorpions: Bioactive Molecules with Promising Therapeutic Potential.","authors":"Kaiyun Xin, Ruize Sun, Wanyang Xiao, Weijie Lu, Chenhui Sun, Jietao Lou, Yanyan Xu, Tianbao Chen, Di Wu, Yitian Gao","doi":"10.3390/toxins17030114","DOIUrl":"10.3390/toxins17030114","url":null,"abstract":"<p><p>Scorpion venom peptides, particularly those derived from Asian species, have garnered significant attention, offering therapeutic potential in pain management, cancer, anticoagulation, and infectious diseases. This review provides a comprehensive analysis of scorpion venom peptides, focusing on their roles as voltage-gated sodium (Nav), potassium (Kv), and calcium (Cav) channel modulators. It analyzed Nav1.7 inhibition for analgesia, Kv1.3 blockade for anticancer activity, and membrane disruption for antimicrobial effects. While the low targeting specificity and high toxicity of some scorpion venom peptides pose challenges to their clinical application, recent research has made strides in overcoming these limitations. This review summarizes the latest progress in scorpion venom peptide research, discussing their mechanisms of action, therapeutic potential, and challenges in clinical translation. This work aims to provide new insights and directions for the development of novel therapeutic drugs.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resilience to Climate Change by Biocontrol Yeasts Against Ochratoxin A Production in Robusta Coffee.","authors":"Claudia López-Rodríguez, Carol Verheecke-Vaessen, Caroline Strub, Angélique Fontana, Tagro Guehi, Sabine Schorr-Galindo, Angel Medina","doi":"10.3390/toxins17030110","DOIUrl":"10.3390/toxins17030110","url":null,"abstract":"<p><p><i>Aspergillus carbonarius</i> is the main producer of Ochratoxin A (OTA) in coffee. In the last few years, there has been an increasing interest in using yeast isolates as Biocontrol Agents to prevent OTA production in coffee cherries during the primary postharvest processing. Little is known about how climate change abiotic conditions of increased temperature (+2-4 °C), elevated CO₂ (existing levels of 400 vs. 1000 ppm), and increased drought stress will impact biocontrol resilience. This study examined the effect of a three-way interaction between temperature (27, 30, and 33 °C) x water activity (a_w) (0.90 and 0.95 a_w) x CO₂ level (400 vs. 1000 ppm) on the growth and OTA production of <i>A. carbonarius</i> and the resilience of three yeast strains' biocontrol capacity on fresh coffee cherries. High a_w (0.95), CO₂, and temperature levels increased the production of OTA by <i>A. carbonarius</i>. All the yeast biocontrol strains significantly reduced <i>A. carbonarius</i> growth by at least 20% and OTA production by up to 85%. From the three strains used, the <i>Meyerozyma caribbica</i> strain (Y4) showed the best resilience to climate change, since it reduced both growth (50%) and OTA production (70%) under future scenarios of CO₂ and a_w at all temperatures tested, and should be the one selected for pilot scale experiments in Ivory Coast.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tolerance to a Diet of Toxic <i>Microcystis aeruginosa</i> in <i>Caenorhabditis elegans</i>.","authors":"Jordan Balson, Jeffrey R Boudreau, Ian D Chin-Sang, Yuxiang Wang, Daniel D Lefebvre","doi":"10.3390/toxins17030109","DOIUrl":"10.3390/toxins17030109","url":null,"abstract":"<p><p>Reported incidences of cyanobacterial harmful algal blooms (CHABs) are increasing across the world due to climate change and nutrient loading, dominating freshwater ecosystems and producing dangerous cyanotoxins that cause ecological damage. <i>Microcystis aeruginosa</i> is one of the most common species of cyanobacteria; it produces hepatotoxic and neurotoxic microcystin-LR. The ecological and human impact of algal blooms is immense, and traditional CHAB remediation methods are not always adequate in eutrophic regions such as Lake Erie in North America. As a result, a proactive, targeted approach is needed to bioremediate cyanobacteria in their pre-colonial stages. Nematodes, such as the model organism <i>Caenorhabditis elegans</i>, are potential candidates for bioremediating cyanobacteria such as <i>M. aeruginosa</i>. <i>C. elegans</i> have metabolic pathways that could detoxify microcystin-LR and enable tolerance to cyanobacteria in nature. We analyzed <i>C. elegans</i> health and fat accumulation on a diet of toxic <i>M. aeruginosa</i> and found that <i>C. elegans</i> can ingest, digest, metabolize, and survive off of this diet. The mean lifespans of the worm populations were only slightly different at 20.68 ± 0.35 (mean ± S.E.M) and 17.89 ± 0.40 when fed <i>E. coli</i> and toxic <i>M. aeruginosa</i>, respectively. In addition, a diet of toxic <i>M. aeruginosa</i> compared to <i>E. coli</i> did not have any significant impact on <i>C. elegans</i> pharyngeal pumping (304.2 ± 9.3 versus 330.0 ± 10.4 pumps/min), dauer response (86.3 ± 1.0 versus 83.65 ± 1.0% in dauer), mobility (209.25 ± 7.0 versus 210.15 ± 4.4 thrashes/min), or SKN-1 expression based on SKN1::GFP fluorescence measurements. Overall, a diet of toxic <i>M. aeruginosa</i> was able to sustain <i>C. elegans</i> development, and <i>C. elegans</i> was tolerant of it. These results suggest that <i>C. elegans</i> and similar nematodes could be viable candidates for cyanobacterial bioremediation.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and Energetic Evidence Supports the Non-Covalent Phosphate Cyclization by the Class II Phospholipase D from <i>Loxosceles intermedia</i>.","authors":"Carolina Gismene, José Fernando Ruggiero Bachega, Daniel Z Doherty, Silvio Sanches Veiga, Raghuvir K Arni, Jorge Enrique Hernández González","doi":"10.3390/toxins17030111","DOIUrl":"10.3390/toxins17030111","url":null,"abstract":"<p><p>Phospholipase D (PLD) enzymes from <i>Loxosceles</i> spider venom mediate envenomation pathology by cleaving phospholipid headgroups. We revisited the crystal structure of <i>Loxosceles intermedia</i> PLD (PDB: 3RLH) to evaluate two alternative mechanisms-covalent and non-covalent-for headgroup cleavage. The covalent mechanism involves a nucleophilic attack on the substrate's P atom by catalytic histidine, forming a phosphohistidine intermediate. It was originally suggested that this intermediate hydrolyzes, leading to linear phosphates. The non-covalent mechanism relies on the substrate's hydroxyl group performing an intramolecular attack on the P atom, thereby generating a cyclic phosphate. Structural refinement of the crystal structure revealed a cyclic phosphate bound at the active site, replacing previously assigned PEG molecules. This cyclic product, stabilized by His12, His47, and Mg²⁺, provides structural evidence that supports phosphate cyclization. The results of computational analyses, including molecular dynamics and quantum mechanics/molecular mechanics simulations, further support the non-covalent mechanism as the energetically preferred pathway, with a significantly lower activation barrier. Our findings highlight the role of substrate orientation and of the catalytic His residues in transphosphatidylation, advancing our understanding of PLD enzymology and providing insights for the design of inhibitors against <i>Loxosceles</i> envenomation.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structurally Similar Mycotoxins Aflatoxin B₁ and Sterigmatocystin Trigger Different and Distinctive High-Resolution Mutational Spectra in Mammalian Cells.","authors":"Pennapa Thongararm, Marisa Chancharoen, Nutchapong Suwanwong, Somsak Ruchirawat, Mathuros Ruchirawat, Bogdan I Fedeles, Robert G Croy, John M Essigmann","doi":"10.3390/toxins17030112","DOIUrl":"10.3390/toxins17030112","url":null,"abstract":"<p><p>Aflatoxin B₁ (AFB₁) and sterigmatocystin (ST) are mycotoxins that pose significant threats to human and animal health owing to their mutagenic, carcinogenic, and toxic properties. They are structurally similar and widely believed to exert their biological effects via the generation of DNA-damaging epoxides at their respective terminal furan rings. Despite structural identity in the warhead portion of each toxin, this work shows that distal parts of each molecule are responsible for the distinctive mutational fingerprints seen in <i>gpt</i>Δ C57BL/6J mouse embryo fibroblasts (MEFs). The two toxins differ structurally in the puckered cyclopentenone ring of AFB₁ and in the planar xanthone functionality of ST. While both toxins mainly induce GC→TA mutations, the aforementioned differences in structure apparently trigger unique patterns of mutations, as revealed by high-resolution duplex sequencing of MEF genomes. AFB₁ is more mutagenic than ST and displays its transversion mutations in a pattern with primary and secondary hotspots (underscored) in 5'-CGC-3' and 5'-CGG-3' contexts, respectively. ST displays a modest 5'-CGG-3' hotspot while its other GC→TA transversions are more uniformly distributed in a pattern resembling established oxidative stress mutational spectra. This research delineates the mutational spectra of AFB₁ and ST, establishing these patterns as possible early-onset biomarkers of exposure.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}