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In this study, we studied the toxicity mechanisms of OCS using human liver carcinoma (HepG2) cells. The results showed that OCS reduced cell viability in a time- and dose-dependent manner. Compared with that in the control, the level of reactive oxygen species (ROS) was significantly increased in all treated HepG2 cells. We also found that (1) OCS induced damage in the HepG2 cells via the apoptotic signaling pathway, (2) OCS increased intracellular free Ca2+ concentration (&gt;180%), and (3) following exposure to 80 \u03bcM OCS, there was an increase in mitochondrial transmembrane potential (MMP, ~174%), as well as a decrease in ATP levels (&lt;78%). In conclusion, OCS is cytotoxic and can induce apoptosis, in which ROS and mitochondrial dysfunction play important roles; however, the observed increase in MMP appears to indicate that HepG2 is resistant to the toxicity induced by OCS.<\/jats:p>","DOI":"10.3390\/ijerph192114272","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T06:49:02Z","timestamp":1667371742000},"page":"14272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Toxicity Assessment of Octachlorostyrene in Human Liver Carcinoma (HepG2) Cells"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-0875","authenticated-orcid":false,"given":"Guofa","family":"Ren","sequence":"first","affiliation":[{"name":"Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China"},{"name":"State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment Protection and Resource Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangming","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"An","sequence":"additional","affiliation":[{"name":"Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-9347","authenticated-orcid":false,"given":"Yu","family":"Shang","sequence":"additional","affiliation":[{"name":"Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kewen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment Protection and Resource Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s00244-010-9486-5","article-title":"Properties of blood, porphyrins, and exposure to legacy and emerging persistent organic pollutants in surf scoters (Melanitta perspicillata) overwintering on the south coast of British Columbia, Canada","volume":"59","author":"Wilson","year":"2010","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.envint.2009.07.006","article-title":"Bioaccumulation and biotransformation of brominated and chlorinated contaminants and their metabolites in ringed seals (Pusa hispida) and polar bears (Ursus maritimus) from East Greenland","volume":"35","author":"Letcher","year":"2009","journal-title":"Environ. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.scitotenv.2018.07.291","article-title":"Temporal trends of legacy organochlorines in eggs of Canadian Arctic seabirds monitored over four decades","volume":"646","author":"Braune","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/etc.410","article-title":"Tissue residue concentrations of organohalogens and trace elements in adult Pacific salmon returning to the Fraser River, British Columbia, Canada","volume":"30","author":"Kelly","year":"2011","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1016\/j.chroma.2009.05.055","article-title":"Gas chromatographic-mass spectrometric analysis of polychlorostyrene congener mixtures in sediments, human sera and cord sera","volume":"1216","author":"Carrizo","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1289\/ehp.8741","article-title":"Persistent pesticides in human breast milk and cryptorchidism","volume":"114","author":"Damgaard","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Soleman, S.R., Fujitani, T., Fujii, Y., and Harada, K.H. (2020). Levels of Octachlorostyrene in Mothers\u2019 Milk and Potential Exposure Among Infants in Sendai City, Japan 2012. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17093064"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tiv.2007.10.004","article-title":"Induction of oxidative stress in human Chang liver cells by octachlorostyrene, the persistent and bioaccumulative toxicant","volume":"22","author":"Park","year":"2008","journal-title":"Toxicol. In Vitro"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1600-0773.1982.tb00938.x","article-title":"Induction of liver microsomal cytochrome P-450 and associated monooxygenases by octachlorostyrene in the rat","volume":"50","author":"Holme","year":"1982","journal-title":"Acta Pharmacologica et Toxicologica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/toxsci\/kfp130","article-title":"Octachlorostyrene induces cytochrome P450, UDP-glucuronosyltransferase, and sulfotransferase via the aryl hydrocarbon receptor and constitutive androstane receptor","volume":"111","author":"Yanagiba","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.tiv.2017.09.014","article-title":"Agonistic effects of diverse xenobiotics on the constitutive androstane receptor as detected in a recombinant yeast-cell assay","volume":"46","author":"Kamata","year":"2018","journal-title":"Toxicol. In Vitro"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1007\/s12272-009-2111-3","article-title":"Whole genomic expression analysis of octachlorostyrene-induced chronic toxicity in Caenorhabditis elegans","volume":"32","author":"Kim","year":"2009","journal-title":"Arch. Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-1-4939-7477-1_9","article-title":"Cell Death and Survival Assays","volume":"1709","author":"Kabakov","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ros in the brain: From physiology to neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.tcb.2020.03.002","article-title":"The complex interplay between antioxidants and ROS in cancer","volume":"30","author":"Harris","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0355-7","article-title":"Mitochondrial dysfunction and oxidative stress in heart disease","volume":"51","author":"Peoples","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rao, L.G., Kang, N.N., and Rao, A.V. (2014). Lycopene and Other Antioxidants in the Prevention and Treatment of Osteoporosis in Postmenopausal Women. Aging, Academic Press. Chapter 24.","DOI":"10.1016\/B978-0-12-405933-7.00024-X"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101084","DOI":"10.1016\/j.redox.2018.101084","article-title":"ROS and the DNA damage response in cancer","volume":"25","author":"Srinivas","year":"2019","journal-title":"Redox Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149180","DOI":"10.1016\/j.scitotenv.2021.149180","article-title":"Effects of polystyrene and triphenyl phosphate on growth, photosynthesis and oxidative stress of Chaetoceros meulleri","volume":"797","author":"Wang","year":"2021","journal-title":"Sci, Total Environ."},{"key":"ref_20","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2019","journal-title":"Alex. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1515\/BC.2009.033","article-title":"Glutathione dysregulation and the etiology and progression of human diseases","volume":"390","author":"Ballatori","year":"2009","journal-title":"Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110051","DOI":"10.1016\/j.jenvman.2019.110051","article-title":"Combined application of biochar and sulfur regulated growth, physiological, antioxidant responses and Cr removal capacity of maize (Zea mays L.) in tannery polluted soils","volume":"259","author":"Bashir","year":"2020","journal-title":"J. Environ. Manag."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1007\/s11064-016-2147-y","article-title":"Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway","volume":"42","author":"Wang","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3389\/fphar.2014.00196","article-title":"Glutathione: New roles in redox signaling for an old antioxidant","volume":"5","author":"Aquilano","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ari, C., Pilla, R., and D\u2019Agostino, D. (2015). Nutritional\/Metabolic Therapies in Animal Models of Amyotrophic Lateral Sclerosis, Alzheimer\u2019s Disease, and Seizures. Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease, Academic Press.","DOI":"10.1016\/B978-0-12-411462-3.00047-3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/B978-0-444-63916-5.00019-7","article-title":"Dementia","volume":"159","author":"Taylor","year":"2018","journal-title":"Handb Clin. Neurol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112183","DOI":"10.1016\/j.ecoenv.2021.112183","article-title":"Flurochloridone induces Sertoli cell apoptosis through ROS-dependent mitochondrial pathway","volume":"216","author":"Sun","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rossmann, M.P., Dubois, S.M., Agarwal, S., and Zon, L.I. (2021). Mitochondrial function in development and disease. Dis. Model. Mech., 14.","DOI":"10.1242\/dmm.048912"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.semcancer.2021.06.002","article-title":"Arsenite impinges on endoplasmic reticulum-mitochondria crosstalk to elicit mitochondrial ROS formation and downstream toxicity","volume":"76","author":"Cantoni","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112549","DOI":"10.1016\/j.ecoenv.2021.112549","article-title":"BDE-47 induces nephrotoxicity through ROS-dependent pathways of mitochondrial dynamics in PK15 cells","volume":"222","author":"Sun","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9246495","DOI":"10.1155\/2019\/9246495","article-title":"An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease","volume":"2019","author":"McMinn","year":"2019","journal-title":"J. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173193","DOI":"10.1016\/j.ejphar.2020.173193","article-title":"Geranylgeranyl acetone prevents glutamate-induced cell death in HT-22 cells by increasing mitochondrial membrane potential","volume":"883","author":"Sugano","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13048-017-0344-1","article-title":"Low oxygen tension increases mitochondrial membrane potential and enhances expression of antioxidant genes and implantation protein of mouse blastocyst cultured in vitro","volume":"10","author":"Ma","year":"2017","journal-title":"J. Ovarian Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.canlet.2016.08.027","article-title":"The repopulating cancer cells in melanoma are characterized by increased mitochondrial membrane potential","volume":"382","author":"Lee","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Thiel, G., Schmidt, T., and Rossler, O.G. (2021). Ca(2+) Microdomains, Calcineurin and the Regulation of Gene Transcription. Cells, 10.","DOI":"10.3390\/cells10040875"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ceca.2016.04.005","article-title":"Intracellular Ca(2+) signaling and Ca(2+) microdomains in the control of cell survival, apoptosis and autophagy","volume":"60","author":"Roest","year":"2016","journal-title":"Cell Calcium"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Barak, P., and Parekh, A.B. (2020). Signaling through Ca(2+) Microdomains from Store-Operated CRAC Channels. Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a035097"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fonc.2017.00073","article-title":"Ca(2+) Microdomains in T-Lymphocytes","volume":"7","author":"Wolf","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s12012-019-09518-9","article-title":"Combustion Particle-Induced Changes in Calcium Homeostasis: A Contributing Factor to Vascular Disease?","volume":"19","author":"Holme","year":"2019","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Brinchmann, B.C., Le Ferrec, E., Podechard, N., Lagadic-Gossmann, D., Shoji, K.F., Penna, A., Kukowski, K., Kubatova, A., Holme, J.A., and Ovrevik, J. (2018). Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051429"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1021\/acs.est.8b00512","article-title":"Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco\/Endoplasmic Reticulum Ca(2+) Dynamics","volume":"52","author":"Zheng","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"330","DOI":"10.18632\/aging.100459","article-title":"Role of Apoptosis in disease","volume":"4","author":"Favaloro","year":"2012","journal-title":"Aging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.3892\/or.2020.7675","article-title":"Neferine induces apoptosis by modulating the ROSmediated JNK pathway in esophageal squamous cell carcinoma","volume":"44","author":"An","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.envpol.2019.05.026","article-title":"Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production","volume":"251","author":"Kang","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.mencom.2017.09.002","article-title":"Halogenated (F, Cl) 1,3-benzodiazoles, 1,2,3-benzotriazoles, 2,1,3-benzothia(selena)diazoles and 1,4-benzodiazines inducing Hep2 cell apoptosis","volume":"27","author":"Prima","year":"2017","journal-title":"Mendeleev. Commun."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/21\/14272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:07:22Z","timestamp":1760144842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/21\/14272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":45,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijerph192114272"],"URL":"https:\/\/doi.org\/10.3390\/ijerph192114272","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}