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Here we investigated BDE-47-triggered DNA damage using HepG2 cells and C3H\/He mice. BDE-47 exposure markedly elevated DNA damage-related \u03b3-H2AX foci in mouse liver. Cellular tests further validated BDE-47-induced DNA damage, manifested as elevated \u03b3-H2AX foci, a higher comet tail DNA percentage, and a longer tail length. Mechanistically, BDE-47 activated the aryl hydrocarbon receptor (AHR) and raised hepatic reactive oxygen species (ROS) and malondialdehyde levels. In cellular assays, antioxidants alleviated DNA damage, whereas AHR inhibitors suppressed ROS overproduction. BDE-47 also upregulated hepatic CYP1A1\/2, whose expression positively correlated with the severity of hepatic DNA injury in mice. In conclusion, BDE-47 exposure induces hepatocellular DNA damage, and its mechanism of action is closely associated with AHR-mediated oxidative stress and CYP1A1\/2 upregulation, which offers new experimental evidence to clarify the hepatotoxic and genotoxic mechanisms of BDE-47.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c07240","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:13:52Z","timestamp":1787066032000},"page":"26735-26744","source":"Crossref","is-referenced-by-count":0,"title":["Chronic BDE-47\nExposure Induces DNA Damage in Hepatocytes:\nInvolvement of Oxidative Stress and CYP1A1\/2 Upregulation"],"prefix":"10.1021","volume":"74","author":[{"given":"Huajun","family":"Zhong","sequence":"first","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieqiu","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8940-7117","authenticated-orcid":true,"given":"Suli","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyuan","family":"Bian","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijian","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Deng","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Su","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chulin","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1699-1307","authenticated-orcid":true,"given":"Guimiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"2026090104482657200_cit1","doi-asserted-by":"publisher","first-page":"101274","DOI":"10.1016\/j.fochx.2024.101274","article-title":"Germany\u2019s first\nTotal Diet Study - Occurrence of non-dioxin-like polychlorinated biphenyls\nand polybrominated diphenyl ethers in foods","volume":"22","author":"Stadion","year":"2024","journal-title":"Food Chem. 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Mater."},{"issue":"3","key":"2026090104482657200_cit23","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/em.22479","article-title":"AOP Report: Development of an Adverse Outcome Pathway\nfor Oxidative DNA Damage Leading to Mutations and Chromosomal Aberrations","volume":"63","author":"Cho","year":"2022","journal-title":"Environ. Mol. Mutagen."},{"issue":"4","key":"2026090104482657200_cit24","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1007\/s00204-026-04317-y","article-title":"Towards a Validation\nof the Standard\nand Enzyme-Linked Comet Assay: A Retrospective Variability Analysis","volume":"100","author":"M\u00f8ller","year":"2026","journal-title":"Arch. 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Immunol."},{"issue":"1","key":"2026090104482657200_cit27","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3390\/ijms24010128","article-title":"Malondialdehyde as an Important Key\nFactor of Molecular Mechanisms of Vascular Wall Damage under Heart\nDiseases Development","volume":"24","author":"Lankin","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2026090104482657200_cit28","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jhazmat.2016.01.025","article-title":"Hazards\nof Low Dose Flame-Retardants\n(BDE-47 and BDE-32): Influence on Transcriptome Regulation and Cell\nDeath in Human Liver Cells","volume":"308","author":"Saquib","year":"2016","journal-title":"J. Hazard. Mater."},{"issue":"1","key":"2026090104482657200_cit29","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41392-026-02583-x","article-title":"Reactive Oxygen Species\n(ROS) in Cancer: From Mechanism to Therapeutic Implications","volume":"11","author":"Akter","year":"2026","journal-title":"Signal Transduct. Target Ther."},{"key":"2026090104482657200_cit30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1146\/annurev-biochem-032620-105820","article-title":"DNA-Protein Crosslinks and Their\nResolution","volume":"91","author":"Weickert","year":"2022","journal-title":"Annu. Rev. Biochem."},{"issue":"6","key":"2026090104482657200_cit31","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1159\/000524186","article-title":"Innate Immune\nResponses to RSV Infection Facilitated by OGG1, an Enzyme Repairing\nOxidatively Modified DNA Base Lesions","volume":"14","author":"Zheng","year":"2022","journal-title":"J. Innate\nImmun."},{"issue":"2","key":"2026090104482657200_cit32","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3390\/toxics14020136","article-title":"AHR-CYP1A1 Axis Perturbation and Necroptosis in 1,2-Dichloroethane\nHepatotoxicity: Elucidation by an Integrated Network Toxicology and\nIn Vitro Validation","volume":"14","author":"Liu","year":"2026","journal-title":"Toxics."},{"key":"2026090104482657200_cit33","doi-asserted-by":"publisher","first-page":"106989","DOI":"10.1016\/j.envint.2021.106989","article-title":"Unraveling the Differential Impact of PAHs and Dioxin-Like\nCompounds on AKR1C3 Reveals the EGFR Extracellular Domain as a Critical\nDeterminant of the AHR Response","volume":"158","author":"Vogeley","year":"2022","journal-title":"Environ. Int."},{"key":"2026090104482657200_cit34","doi-asserted-by":"publisher","first-page":"116314","DOI":"10.1016\/j.taap.2022.116314","article-title":"Oxidative Stress Modulates\nExpression of Immune Checkpoint Genes\nvia Activation of AhR Signaling","volume":"457","author":"Kou","year":"2022","journal-title":"Toxicol. Appl.\nPharmacol."},{"key":"2026090104482657200_cit35","doi-asserted-by":"publisher","first-page":"5213186","DOI":"10.1155\/2017\/5213186","article-title":"\u03b2-Naphthoflavone-Induced\nMitochondrial Respiratory Damage in Cyp1 Knockout Mouse and in Cell\nCulture Systems: Attenuation by Resveratrol Treatment","volume":"2017","author":"Anandasadagopan","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"2026090104482657200_cit36","doi-asserted-by":"publisher","first-page":"123675","DOI":"10.1016\/j.envpol.2024.123675","article-title":"Particulate Matter Stimulates the NADPH Oxidase System\nvia AhR-Mediated Epigenetic Modifications","volume":"347","author":"Kang","year":"2024","journal-title":"Environ.\nPollut."},{"key":"2026090104482657200_cit37","doi-asserted-by":"publisher","first-page":"147171","DOI":"10.1016\/j.gene.2023.147171","article-title":"Genic-Intergenic Polymorphisms\nof CYP1A Genes and Their Clinical Impact","volume":"857","author":"Kukal","year":"2023","journal-title":"Gene."},{"issue":"5","key":"2026090104482657200_cit38","doi-asserted-by":"publisher","first-page":"100285","DOI":"10.1016\/j.dmd.2026.100285","article-title":"Transcriptomic\nand Metabolite-Centric Profiling Reveal Aryl Hydrocarbon Receptor-Mediated\nCytochrome P450 1A1 Autoinduction of the Selective Modulator PM-4321","volume":"54","author":"Kumar","year":"2026","journal-title":"Drug Metab. 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Saf."},{"key":"2026090104482657200_cit41","doi-asserted-by":"publisher","first-page":"152566","DOI":"10.1016\/j.tox.2020.152566","article-title":"Estragole: DNA Adduct\nFormation in Primary Rat Hepatocytes and Genotoxic Potential in HepG2-CYP1A2\nCells","volume":"444","author":"Schulte-Hubbert","year":"2020","journal-title":"Toxicology"},{"issue":"2","key":"2026090104482657200_cit42","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/toxsci\/kfh284","article-title":"Effects\nof Polybrominated Diphenyl Ethers on Basal and TCDD-Induced Ethoxyresorufin\nActivity and Cytochrome P450\u20131A1 Expression in MCF-7, HepG2,\nand H4IIE Cells","volume":"82","author":"Peters","year":"2004","journal-title":"Toxicol. Sci."},{"issue":"1","key":"2026090104482657200_cit43","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/toxsci\/kfj186","article-title":"Interactions\nof Polybrominated Diphenyl Ethers with the Aryl Hydrocarbon Receptor\nPathway","volume":"92","author":"Peters","year":"2006","journal-title":"Toxicol. Sci."},{"issue":"5","key":"2026090104482657200_cit44","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S0006-2952(00)00543-8","article-title":"Repression of Cytochrome\nP450 1A1 Gene Expression by Oxidative Stress:\nMechanisms and Biological Implications","volume":"61","author":"Barouki","year":"2001","journal-title":"Biochem.\nPharmacol."},{"issue":"12","key":"2026090104482657200_cit45","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1021\/acs.chemrestox.2c00238","article-title":"Butyrate Enhances\n\u03b3-H2AX\nInduced by Benzo[a]pyrene","volume":"35","author":"Tanaka","year":"2022","journal-title":"Chem. Res. 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