Food and Chemical Toxicology最新文献

{"title":"Multi-Omics Reveals PM2.5-Associated Neuronal Disulfidptosis: SLC3A2-OXSM Imbalance, Immune Dysregulation, and Electrophysiological Dysfunction.","authors":"Lina He, Dongmei Li, Xing Wei, Xiaojuan Wang, Yingying Cao, Muhua Zhou, Kunmei He, Junrui He, Xibao Luo","doi":"10.1016/j.fct.2026.116147","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116147","url":null,"abstract":"<p><p>Particulate matter 2.5 (PM2.5) is a major environmental pollutant linked to neurological disorders through poorly understood mechanisms. We investigated whether PM2.5 induces disulfidptosis, a novel form of regulated cell death characterized by NADPH depletion and disulfide stress, in neuronal cells. Combining bioinformatics analysis of a PM2.5-exposed human cohort (GSE60767, n=466) with in vitro experiments in primary neurons and in vivo validation in rats, we identified a characteristic molecular signature featuring SLC3A2 upregulation and OXSM downregulation (p<0.01). This imbalance was associated with significant immune dysregulation (elevated memory B cells, CD8⁺ T cells, and Tregs; reduced monocytes) and metabolic disturbances (NADP+/NADPH imbalance, cystine overload). Direct evidence from non-reducing western blot confirmed disulfide-mediated actin crosslinking in both cultured neurons and hippocampal tissues of PM2.5-exposed rats. Lentiviral manipulation revealed a unidirectional regulatory relationship wherein SLC3A2 knockdown (RNAi-SLC3A2) increased OXSM expression, while OXSM overexpression (OE-OXSM) did not affect SLC3A2 levels. Both RNAi-SLC3A2 and OE-OXSM interventions improved neuronal survival and normalized NADP+/NADPH ratios after PM2.5 exposure (200 μg/mL). However, RNAi-SLC3A2 significantly inhibited cystine uptake. Correspondingly, RNAi-SLC3A2 demonstrated more robust neuroprotection compared to OE-OXSM, as evidenced by greater improvements in neuronal viability and complete restoration of action potential amplitude. Collectively, these findings establish that PM2.5 induces neuronal disulfidptosis through hierarchical SLC3A2-OXSM axis dysregulation and identify this unidirectional relationship as a novel therapeutic target for PM2.5-associated neurological injury.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116147"},"PeriodicalIF":3.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Evaluation of Peptide Compound TSC6: A 13-Week Subchronic Toxicity and Genotoxicity Study.","authors":"Genwei Zhang, Xiaolu Huang, Yujie Fang, Tongren Liu, Congling Fan, Bo Li, Lipeng Lai","doi":"10.1016/j.fct.2026.116131","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116131","url":null,"abstract":"<p><p>TSC6-peptide is an 8-amino acid synthetic peptide compound that inhibits intestinal α-amylase upon oral administration to control the digestion and absorption of starchy foods. However, its toxicological safety and other scientific evidence remain to be established. Given the potential utility of TSC6-peptide as an α-amylase inhibitor, this study conducted in vivo and in vitro experiments to support its safety profile. In reverse mutation and mammalian micronucleus assays revealed no genotoxicity for TSC6-peptide. Meanwhile, in the 90-day dietary toxicity study in rats, the NOAEL was 500 mg/kg bw/day for male rats following TSC6-peptide administration and the LOAEL for female rats was 50 mg/kg bw/day. These results indicate that TSC6-peptide possesses controllable safety as an α-amylase inhibitor.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116131"},"PeriodicalIF":3.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIFM fragrance ingredient safety assessment, ethyl octadecanoate, CAS Registry Number 111-61-5.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116130","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116130","url":null,"abstract":"<p><p>Ethyl octadecanoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that ethyl octadecanoate is not genotoxic. Data on ethyl octadecanoate provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data from read-across analog methyl hexadecanoate (CAS # 112-39-0) provided ethyl octadecanoate a No Expected Sensitization Induction Level (NESIL) of 2400 μg/cm² for the skin sensitization endpoint. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; ethyl octadecanoate is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to ethyl octadecanoate is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; ethyl octadecanoate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), based on its current volume of use (VoU) in Europe (EU), North America (NA), Asia-Pacific (AP), and South America (SA) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116130"},"PeriodicalIF":3.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIFM fragrance ingredient safety assessment, sclareol, CAS Registry Number 515-03-7.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116133","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116133","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116133"},"PeriodicalIF":3.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circS100A11 regulates PKD1-mediated food allergy through recruiting EIF4A3.","authors":"Jun Li, Jizhi Xu, Xiaoju Tang, Lingling Chen, Yan Huang, Tengfei Huang, Tuanmei Wang, Xiaohui Gong","doi":"10.1016/j.fct.2026.116108","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116108","url":null,"abstract":"<p><strong>Background: </strong>Food allergy is a potentially serious immune system reaction that significantly impacts the quality of life for individuals. Studies have shown that dysregulation of circular RNAs (circRNAs) mediates the activation of immune cells and inflammatory mechanisms in allergic diseases. This study aimed to elucidate its functions and the pathways involved in food allergic reactions.</p><p><strong>Methods: </strong>A Th2-polarized food allergy model was established in BALB/c mice using ovalbumin (OVA) adsorbed to aluminum hydroxide. Allergic responses were evaluated using a combination of clinical scoring, histology (H&E), and transmission electron microscopy (TEM). Serum IgE and cytokines (IL-4, IL-5, IL-13) were measured by ELISA. Molecular expressions were analyzed by western blot and qRT-PCR. RNA immunoprecipitation (RIP) and PAR-CLIP assays validated RNA-protein interactions.</p><p><strong>Results: </strong>circS100A11, EIF4A3, and PKD1 was upregulated in sensitized mice. EIF4A3 was found to bind to and stabilized PKD1 mRNA, and its overexpression exacerbated allergic reactions in a PKD1-dependent manner. circS100A11 was found to directly interact with EIF4A3, promoting the recruitment of EIF4A3 to the PKD1 transcript. circS100A11 knockdown alleviated allergy, which was reversed by EIF4A3 overexpression. The detrimental effects of the circS100A11/EIF4A3 axis were abolished by concurrent PKD1 knockdown.</p><p><strong>Conclusion: </strong>Our findings define a novel regulatory pathway in which circS100A11 aggravates food allergy by recruiting EIF4A3 to enhance PKD1 expression, presenting a potential therapeutic target for intervention.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116108"},"PeriodicalIF":3.5,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the effects of gestational arsenic exposure on the developmental toxicity of brain tissue in mice offspring using network toxicology and RNA-seq","authors":"Zitong Wang ,&nbsp;Wenjin Qiao ,&nbsp;Ruigang Liu ,&nbsp;Yuan Lv ,&nbsp;Binjie Niu ,&nbsp;Tianxu Li ,&nbsp;Mengling Zhang ,&nbsp;Yanhui Xiang ,&nbsp;Rui Qiao ,&nbsp;Dapeng Tai","doi":"10.1016/j.fct.2026.116001","DOIUrl":"10.1016/j.fct.2026.116001","url":null,"abstract":"<div><h3>Background</h3><div>Long-term arsenic exposure is associated with health risks, including neurotoxicity, cardiovascular diseases, and cancer, with heightened vulnerability during early development. This study integrates RNA sequencing (RNA-seq) and network toxicology to construct a competing endogenous RNA (ceRNA) network and elucidate molecular mechanisms of prenatal arsenic-induced neurodevelopmental toxicity.</div></div><div><h3>Methods</h3><div>Pregnant ICR mice were exposed to sodium arsenite (NaAsO₂, 0.5 ppm) through drinking water. Behavioral tests were performed on postnatal day 30 (PND 30). A total of 20 offspring mice (male/female = 1:1) underwent behavioral assessments, including open field, forced swim, and tail suspension tests, to evaluate anxiety- and depression-like behaviors. Neonatal brain tissues were collected on postnatal day 1 (PND 1) and analyzed using RNA sequencing. The results were further integrated with network toxicology analyses and were subsequently validated experimentally.</div></div><div><h3>Results</h3><div>Prenatal arsenic exposure elicited significant anxiety- and depression-like behaviors in offspring. Integrated analyses showed that disrupted ceRNA regulatory axes converge the calcium-signaling pathway, neuroactive ligand–receptor interaction, and synaptic-vesicle cycle, revealing key molecular mechanisms underlying the observed neurodevelopmental impairments.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that prenatal arsenic exposure induces early molecular perturbations in the neonatal brain by altering competing endogenous RNA regulatory networks. More importantly, the integration of transcriptomic data with network-based analyses provides a systematic framework for elucidating the underlying mechanisms of developmental neurotoxicity, highlighting key signaling pathways associated with synaptic function and neuronal communication. This network-oriented approach offers mechanistic insights beyond single-gene analysis and facilitates the identification of critical regulatory processes involved in arsenic-induced neurodevelopmental effects.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116001"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FEMA GRAS assessment of natural flavor complexes: Pepper, ginger, coniferous-derived and related flavoring ingredients","authors":"Stephen S. Hecht ,&nbsp;Samuel M. Cohen ,&nbsp;Gerhard Eisenbrand ,&nbsp;Shoji Fukushima ,&nbsp;Nigel J. Gooderham ,&nbsp;F. Peter Guengerich ,&nbsp;Ivonne M.C.M. Rietjens ,&nbsp;Thomas J. Rosol ,&nbsp;Jeanne M. Davidsen ,&nbsp;Christie L. Harman ,&nbsp;Sean V. Taylor","doi":"10.1016/j.fct.2025.115849","DOIUrl":"10.1016/j.fct.2025.115849","url":null,"abstract":"<div><div>As part of the Expert Panel of the Flavor and Extract Manufacturers Association's (FEMA) program to evaluate the safety of flavor ingredients, this publication, thirteenth in the series, details the re-evaluation of natural flavor complexes (NFCs) whose constituent profiles are characterized by mono- and sesquiterpene hydrocarbons. The Panel's constituent-based safety evaluation procedure parses the identified constituents of each NFC into well-defined congeneric groups. For each congeneric group, an evaluation based on the estimated intake is conducted using the conservative Threshold of Toxicological Concern (TTC) approach and a review of available data on absorption, metabolism and toxicity, including genotoxicity, for identified constituents and the NFCs, is conducted. The scope of the safety evaluation of the NFCs contained herein does not include added use in dietary supplements or any products other than food. Thirty-five NFCs, derived from the <em>Angelica, Abies, Cananga, Croton, Apium, Canarium, Erigeron</em>, <em>Ferula, Zingiber, Humulus, Juniperus, Cistus, Commiphora, Boswellia, Piper, Pinus</em> and <em>Schinus</em> genera were determined/affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115849"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic and in silico characterization identifies conarachin as a major IgE-reactive peanut allergen","authors":"Hanène Djeghim ,&nbsp;Ouided Benslama ,&nbsp;Ines Bellil ,&nbsp;Postigo Idoia ,&nbsp;Patricia Sanchez ,&nbsp;Douadi Khelifi ,&nbsp;Huda Alsaeedi ,&nbsp;Mikhael Bechlany ,&nbsp;Ahmed Barhoum","doi":"10.1016/j.fct.2026.116017","DOIUrl":"10.1016/j.fct.2026.116017","url":null,"abstract":"<div><div>Peanut allergy is a major health issue, and detailed molecular insights are essential to understand allergenicity. In this study, an integrated immunoproteomic and in silico docking workflow was applied to characterize allergens from six Algerian peanut varieties. Protein profiling by 2-DE (pI 4.8-10.1, 9-68 kDa), followed by immunoblotting, revealed strong IgE binding to low-molecular-weight proteins (20-25 kDa). Sixteen distinct protein spots were excised and analyzed by LC-MS/MS, identifying key allergens including Ara h 1, Ara h 2, Ara h 3, and Ara h 6, with peptide coverages ranging from 34% (Ara h 1) to 70% (Ara h 2). Four highly reactive allergens were prioritized, and nine were further investigated through molecular docking against the human IgE receptor. Computational analyses uncovered novel epitope interactions, with conarachin (Q647H1) emerging as the strongest binder (cluster score −625.4), showing stable contacts at epitopes 26-50, 112-151, and 185-491. Chain-specific docking highlighted high affinity toward both IgE heavy and light chains, underlining its structural adaptability.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116017"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limosilactobacillus fermentum LF61: A multidimensional study on safety and functionality from genomics to clinical application","authors":"Manfei Jin ,&nbsp;Fei Xu ,&nbsp;Yinhua Liu ,&nbsp;Zhao Jiang","doi":"10.1016/j.fct.2026.116002","DOIUrl":"10.1016/j.fct.2026.116002","url":null,"abstract":"<div><div>This study presents a comprehensive multidimensional assessment of the safety and functional efficacy of <em>Limosilactobacillus fermentum</em> LF61, a strain isolated from human milk. Genomic analysis revealed no virulence factors (VFDB), drug resistance genes (CARD), or toxin synthesis gene cluster (antiSMASH) within its chromosome (2.04 Mb) and plasmid (15.5 kb), meeting EFSA's QPS safety criteria. In vitro studies demonstrated that LF61 exhibited a 2-h survival rate of &gt;98% in gastric acid (pH 2.0) and a survival rate of 99.66% in intestinal fluid (pH 8.0). LF61 was also nontoxic to Caco-2 cells (metabolic activity at 20% concentration: 100.3 ± 2.1%). An acute oral toxicity test (in ICR mice) demonstrated an LD50 &gt; 2 × 10¹⁰ CFU/kg. In a randomized, double-blind clinical trial (n = 49), daily intake of 3 × 10¹⁰ CFU of LF61 for 8 weeks increased serum levels of the antimicrobial peptide LL-37 by 12.3% (<em>p</em> &lt; 0.05), and IgA, IgG, and IgM by 18.7%, 15.2%, and 9.8%, respectively (<em>p</em> &lt; 0.05). Metagenomic analysis revealed that LF61 promoted colonization by short-chain fatty acid-producing bacteria, such as <em>Mitsuokella</em> and <em>Turicibacter</em> (LDA &gt;3), activated the carbohydrate metabolism pathway (<em>p</em> = 0.002), and maintained stable α-diversity in the microbiome (Shannon index <em>p</em> &gt; 0.05). Collectively, our findings indicate that LF61 exerts beneficial effects via a gut-immune axis bidirectional regulatory mechanism, offering a theoretical basis and clinical evidence for the development of novel immunomodulatory probiotics targeting the gut-immune axis.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116002"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic exposure induces stemness in human normal breast epithelial cells via the E2F2/FZD10 axis","authors":"Yang Yang ,&nbsp;Dexiu Hu ,&nbsp;Maoyuan Gong ,&nbsp;Xingcan Yang ,&nbsp;Ruobi Chen ,&nbsp;Jingyuan Lin ,&nbsp;Qibing Zeng ,&nbsp;Yuyan Xu","doi":"10.1016/j.fct.2026.116003","DOIUrl":"10.1016/j.fct.2026.116003","url":null,"abstract":"<div><div>Chronic arsenic exposure is associated with systemic toxicity and carcinogenic risk, yet its mechanistic link to breast cancer remains poorly defined. Here, we demonstrate that long-term exposure of human mammary epithelial cells (MCF-10A) to low-dose sodium arsenite (NaAsO₂) drives acquisition of a breast cancer stem-like phenotype. NaAsO₂-exposed cells exhibited enhanced migration (1.34-fold), invasion (2.9-fold), and sphere-formation (1.54-fold) capacities, along with elevated expression of BCSCs markers EpCAM (3.17-fold) and ALDH1 (2.45-fold) and an increased CD44⁺/CD24^-/low subpopulation (1.63-fold). Transcriptomic profiling identified the transcription factor E2F2 as a key mediator of this transformation. Functional studies established that E2F2 directly regulates FZD10 expression, activating the Wnt/β-catenin pathway to sustain the stem-like state. Collectively, we unveil the E2F2/FZD10 axis as a previously unrecognized molecular conduit through which environmental arsenic reprograms mammary epithelial cells toward a BCSCs-like phenotype, providing mechanistic insight into arsenic-associated breast cancer risk and revealing a potential target for preventive intervention.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116003"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}