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The determination of biomarkers such as trans-trans muconic acid (AttM) and S-phenylmercapturic acid (SPMA) show exposure without reflecting the toxic effects of benzene. For this reason, in this study, the urinary metabolome of individuals exposed to low concentrations of benzene was investigated, with the aim of understanding the biological response to exposure to this xenobiotic and identifying metabolites correlated with the toxic effects induced by it. Ultra-efficient liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer (UHPLC-ESI-Q-ToF-MS) was used to identify metabolites in the urine of environmentally (n = 28) and occupationally exposed (n = 32) to benzene (mean of 22.1 \u03bcg\u00b7m\u22123 and 31.8 \u03bcg\u00b7m\u22123, respectively). Non-targeted metabolomics analysis by PLS-DA revealed nine urinary metabolites discriminating between groups and statistically correlated with oxidative damage (MDA, thiol) and genetic material (chromosomal aberrations) induced by the hydrocarbon. The analysis of metabolic pathways revealed important alterations in lipid metabolism. These results point to the involvement of alterations in lipid metabolism in the mechanisms of cytotoxic and genotoxic action of benzene. Furthermore, this study proves the potential of metabolomics to provide relevant information to understand the biological response to exposure to xenobiotics and identify early effect biomarkers.<\/jats:p>","DOI":"10.3390\/metabo12100978","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T02:29:46Z","timestamp":1665973786000},"page":"978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Metabolomic Study of Urine from Workers Exposed to Low Concentrations of Benzene by UHPLC-ESI-QToF-MS Reveals Potential Biomarkers Associated with Oxidative Stress and Genotoxicity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9099-4843","authenticated-orcid":false,"given":"Michele P. R.","family":"Mendes","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9 N.","family":"Paiva","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabele C.","family":"Costa-Amaral","sequence":"additional","affiliation":[{"name":"Center for the Study of Occupational Health and Human Ecology (CESTEH), Sergio Arouca National School of Public Health (ENSP), Oswaldo Cruz Foundation (Fiocruz), Rua Leopoldo Bulh\u00f5es 1480, Manguinhos, Rio de Janeiro 21041-210, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3090-7477","authenticated-orcid":false,"given":"Leandro V. B.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Center for the Study of Occupational Health and Human Ecology (CESTEH), Sergio Arouca National School of Public Health (ENSP), Oswaldo Cruz Foundation (Fiocruz), Rua Leopoldo Bulh\u00f5es 1480, Manguinhos, Rio de Janeiro 21041-210, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor O.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Center for the Study of Occupational Health and Human Ecology (CESTEH), Sergio Arouca National School of Public Health (ENSP), Oswaldo Cruz Foundation (Fiocruz), Rua Leopoldo Bulh\u00f5es 1480, Manguinhos, Rio de Janeiro 21041-210, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6842-3016","authenticated-orcid":false,"given":"Eline S.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Center for the Study of Occupational Health and Human Ecology (CESTEH), Sergio Arouca National School of Public Health (ENSP), Oswaldo Cruz Foundation (Fiocruz), Rua Leopoldo Bulh\u00f5es 1480, Manguinhos, Rio de Janeiro 21041-210, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane L.","family":"Larentis","sequence":"additional","affiliation":[{"name":"Center for the Study of Occupational Health and Human Ecology (CESTEH), Sergio Arouca National School of Public Health (ENSP), Oswaldo Cruz Foundation (Fiocruz), Rua Leopoldo Bulh\u00f5es 1480, Manguinhos, Rio de Janeiro 21041-210, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0840-0810","authenticated-orcid":false,"given":"Leiliane C.","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","first-page":"1129","article-title":"Environmental Exposure to Benzene: An Update","volume":"104","author":"Wallace","year":"1996","journal-title":"Environ. Health Perspect."},{"key":"ref_2","unstructured":"IARC\u2014International Agency for Research on Cancer (2018). Benzene\/IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cbi.2005.03.038","article-title":"Clinical Analysis of 43 Cases of Chronic Benzene Poisoning","volume":"153","author":"Kuang","year":"2005","journal-title":"Chem. Biol. Interact."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1158\/1055-9965.EPI-06-0262","article-title":"Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures","volume":"15","author":"Kim","year":"2006","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/carcin\/bgs382","article-title":"Low-Dose Metabolism of Benzene in Humans: Science and Obfuscation","volume":"34","author":"Rappaport","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/10408444.2012.756455","article-title":"The Use of Biomoni toring Data in Exposure and Human Health Risk Assessment: Benzene Case Study","volume":"43","author":"Arnold","year":"2013","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.toxlet.2018.08.001","article-title":"Biological Monitoring of Low Level Exposure to Benzene in an Oil Re Fi Nery: E Ff Ect of Modulating Factors","volume":"298","author":"Carrieri","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/1354750X.2017.1387935","article-title":"Biological Monitoring of Exposure to Low Concentrations of Benzene in Workers at a Metallurgical Coke Production Plant: New Insights into S-Phenylmercapturic Acid and Urinary Benzene","volume":"23","author":"Lovreglio","year":"2017","journal-title":"Biomarkers"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ejca.2018.04.018","article-title":"Environment, Cancer and Inequalities d the Urgent Need for Prevention","volume":"103","author":"Vineis","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.yrtph.2017.09.002","article-title":"Applying \u2019 Omics Technologies in Chemicals Risk Assessment: Report of an ECETOC Workshop","volume":"91","author":"Buesen","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cotox.2019.03.006","article-title":"ScienceDirect Toxicology Confidence in Metabolite Identification Dictates the Applicability of Metabolomics to Regulatory Toxicology","volume":"16","author":"Malinowska","year":"2020","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_12","first-page":"341","article-title":"The Analytical Process to Search for Metabolomics Biomarkers","volume":"147","author":"Capote","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6362","DOI":"10.1039\/C6AN01753C","article-title":"Strategies for Large-Scale Targeted Metabolomics Quantification by Liquid Chromatography-Mass Spectrometry","volume":"141","author":"Zhou","year":"2016","journal-title":"Analyst"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s11306-020-01665-3","article-title":"Environmental Lipidomics: Understanding the Response of Organisms and Ecosystems to a Changing World","volume":"16","author":"Koelmel","year":"2020","journal-title":"Metabolomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-pharmtox-010818-021315","article-title":"The Exposome: Molecules to Populations","volume":"59","author":"Niedzwiecki","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/aje\/kwu143","article-title":"Practice of Epidemiology Design and Analysis of Metabolomics Studies in Epidemiologic Research: A Primer on -Omic Technologies","volume":"180","author":"Tzoulaki","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12989-016-0160-6","article-title":"Copper Oxide Nanoparticle Toxicity Profiling Using Untargeted Metabolomics","volume":"13","author":"Boyles","year":"2016","journal-title":"Part. Fibre Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1007\/s11356-017-0774-8","article-title":"Metabolomic Analysis of the Toxic Effect of Chronic Exposure of Cadmium on Rat Urine","volume":"25","author":"Chen","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.toxlet.2016.05.003","article-title":"Metabolite pro Fi Les of Rats in Repeated Dose Toxicological Studies after Oral and Inhalative Exposure","volume":"255","author":"Fabian","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jchromb.2015.01.029","article-title":"Combination of Direct Infusion Mass Spectrometry and Gas Chromatography Mass Spectrometry for Toxicometabolomic Study of Red Blood Cells and Serum of Mice Mus Musculus after Mercury Exposure","volume":"985","author":"Navarro","year":"2015","journal-title":"J. Chromatogr. B"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1039\/C4MB00523F","article-title":"The Plasma Metabolic Profiling of Chronic Acephate Exposure in Rats via an Ultra-Performance Liquid Chromatography-Mass Spectrometry Based","volume":"11","author":"Hou","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.envpol.2017.11.073","article-title":"A Metabolomics Strategy to Assess the Combined Toxicity of Polycyclic Aromatic Hydrocarbons ( PAHs ) and Short-Chain Chlorinated Paraf Fi Ns","volume":"234","author":"Wang","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/978-3-030-15950-4_38","article-title":"Analytical Methods for Mass Spectrometry-Based Metabolomics Studies","volume":"1140","author":"Wang","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Emwas, A.-H., Roy, R., McKay, R.T., Tenori, L., Saccenti, E., Gowda, G.A.N., Raftery, D., Alahmari, F., Jaremko, L., and Jaremko, M. (2019). NMR Spectroscopy for Metabolomics Research. Metabolites, 9.","DOI":"10.3390\/metabo9070123"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1021\/ac504075g","article-title":"NMR Spectroscopy for Metabolomics and Metabolic Profiling","volume":"87","author":"Larive","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"22335","DOI":"10.1039\/C8RA01574K","article-title":"Advances in Mass Spectrometry-Based Metabolomics for Investigation of Metabolites","volume":"8","author":"Ren","year":"2018","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jchromb.2019.04.009","article-title":"Untargeted LC\/MS-Based Metabolic Phenotyping (Metabonomics\/Metabolomics): The State of the Art","volume":"1117","author":"Gika","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.trac.2016.07.004","article-title":"Data Analysis Strategies for Targeted and Untargeted LC-MS Metabolomic Studies: Overview and Workflow","volume":"82","author":"Gorrochategui","year":"2016","journal-title":"Trends Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Costa-Amaral, I.C., Carvalho, L.V.B., Santos, M.V.C., Teixeira, L.R., Collins, A.R., de C\u00e1ssia, O.C., Mattos, O.C., and Sarcinelli, P.N. (2019). Environmental Assessment and Evaluation of Oxidative Stress and Genotoxicity Biomarkers Related to Chronic Occupational Exposure to Benzene. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16122240"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cbpa.2015.11.009","article-title":"A Roadmap for the XCMS Family of Software Solutions in Metabolomics","volume":"30","author":"Mahieu","year":"2016","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1021\/ac300698c","article-title":"XCMS Online: A Web-Based Platform to Process Untargeted Metabolomic Data","volume":"84","author":"Tautenhahn","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the Gap between Raw Spectra and Functional Insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed Minimum Reporting Standards for Chemical Analysis","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Venable, W.B., and Ripley, B. (2002). Modern Applied Statistics with S, Springer. [4th ed.].","DOI":"10.1007\/978-0-387-21706-2"},{"key":"ref_35","unstructured":"Akaike, H. Information Theory and an Extension of the Maximum Likelihood Principle. Proceedings of the 2nd International Symposium on Information Theory."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1136\/emermed-2017-206735","article-title":"What Is an ROC Curve?","volume":"34","author":"Hoo","year":"2017","journal-title":"Emerg. Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12265","DOI":"10.1021\/es503659w","article-title":"Urinary Metabolomics Revealed Arsenic Internal Dose-Related Metabolic Alterations: A Proof-of-Concept Study in a Chinese Male Cohort","volume":"48","author":"Zhang","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"ref_38","unstructured":"de Moraes Moreau, R.L., and Bastos de Diqueira, M.E.P. (2016). Toxicologia Anal\u00edtica, Guanabara Koogan. [2nd ed.]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1289\/ehp.7337","article-title":"Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements","volume":"113","author":"Barr","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_40","unstructured":"Brazil Minist\u00e9rio do Trabalho (1995). Norma Regulamentadora (NR) 15\u2014Atividades e Opera\u00e7\u00f5es Insalubres, Minist\u00e9rio do Trabalho. Anexo No. 13-A."},{"key":"ref_41","first-page":"1","article-title":"Normas Ocupacionais Do Benzeno: Uma Abordagem Sobre o Risco e Exposi\u00e7\u00e3o Nos Postos de Revenda de Combust\u00edveis","volume":"6369","author":"Mendes","year":"2017","journal-title":"Rev. Bras. Sa\u00fade Ocup."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/carcin\/bgr297","article-title":"Current Understanding of the Mechanism of Benzene-Induced Leukemia in Humans: Implications for Risk Assessment","volume":"33","author":"Mchale","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1021\/tx9902082","article-title":"Role of Quinones in Toxicology","volume":"13","author":"Bolton","year":"2000","journal-title":"Chem. Res. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lodovici, M., and Bigagli, E. (2011). Oxidative Stress and Air Pollution Exposure. J. Toxicol., 2011.","DOI":"10.1155\/2011\/487074"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mrgentox.2013.04.008","article-title":"Genotoxicity and Oxidative Stress in Gasoline Station Attendants","volume":"754","author":"Moro","year":"2013","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1002\/ajim.20901","article-title":"Exposure to Benzene Induces Oxidative Stress, Alters the Immune Response and Expression of P53 in Gasoline Filling Workers","volume":"53","author":"Uzma","year":"2010","journal-title":"Am. J. Ind. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hussain, T., Tan, B., Yin, Y., Blachier, F., Tossou, M.C.B., and Rahu, N. (2016). Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?. Oxid. Med. Cell. Longev., 2016.","DOI":"10.1155\/2016\/7432797"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","article-title":"Oxidative Stress, Inflammation, and Cancer: How Are They Linked?","volume":"49","author":"Reuter","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and Cancer: Triggers, Mechanisms and Consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/004982599238047","article-title":"\u201cMetabonomics\u201d: Understanding the Metabolic Responses of Living Systems to Pathophysiological Stimuli via Multivariate Statistical Analysis of Biological NMR Spectroscopic Data","volume":"29","author":"Nicholson","year":"1999","journal-title":"Xenobiotica"},{"key":"ref_51","first-page":"3","article-title":"Metabolomics: From Fundamentals to Clinical Applications","volume":"Volume 965","author":"Klassen","year":"2017","journal-title":"Metabolomics: Definitions and Significance in Systems Biology"},{"key":"ref_52","first-page":"75","article-title":"Metabol\u00f4mica: Defini\u00e7\u00f5es, Estado-da-Arte e Aplica\u00e7\u00f5es Representativas","volume":"41","author":"Canuto","year":"2018","journal-title":"Quim. Nova"},{"key":"ref_53","unstructured":"Santana, F.B. (2015). Uso de Espectroscopia No Infravermelho M\u00e9dio e An\u00e1lise Discriminante Por Quadrados M\u00ednimos Parciais Na Determina\u00e7\u00e3o de Adultera\u00e7\u00f5es Em \u00d3leos de Andiroba, Pr\u00edmula e Rosa Mosqueta. [Ph.D. Thesis, Universidade Federal de Uberl\u00e2ndia]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cpbi.86","article-title":"Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis","volume":"68","author":"Chong","year":"2019","journal-title":"Curr. Protoc. Bioinforma."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/elps.201300053","article-title":"From Numbers to a Biological Sense: How the Strategy Chosen for Metabolomics Data Treatment May Affect Final Results. A Practical Example Based on Urine Fingerprints Obtained by LC-MS","volume":"34","author":"Godzien","year":"2013","journal-title":"Electrophoresis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.publhealth.012809.103646","article-title":"Advances in Understanding Benzene Health Effects and Susceptibility","volume":"31","author":"Smith","year":"2010","journal-title":"Annu. Rev. Public Health"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging Applications of Metabolomics in Drug Discovery and Precision Medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-069X-10-S1-S15","article-title":"Future Research Perspectives on Environment and Health: The Requirement for a More Expansive Concept of Translational Cancer Research","volume":"10","author":"Wild","year":"2011","journal-title":"Environ. Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1080\/15287394.2012.699858","article-title":"Metabonomics Biomarkers for Subacute Toxicity Screening for Benzene Exposure in Mice","volume":"75","author":"Sun","year":"2012","journal-title":"J. Toxicol. Environ. Health"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.3390\/ijms15034994","article-title":"Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H \/ He Mice Exposed to Benzene","volume":"15","author":"Sun","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/toxres\/tfab053","article-title":"Lipidomic Analysis Reveals Disturbances in Glycerophospholipid and Sphingolipid Metabolic Pathways in Benzene-Exposed Mice","volume":"10","author":"Yu","year":"2021","journal-title":"Toxicol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.mam.2017.03.003","article-title":"Bile Acid Analysis in Human Disorders of Bile Acid Biosynthesis","volume":"56","author":"Vaz","year":"2017","journal-title":"Mol. Aspects Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile Acid\u2013Microbiota Cross-Talk in Gastrointestinal Inflammation and Carcinogenesis","volume":"15","author":"Jia","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sun, R., Xu, K., Ji, S., Pu, Y., Man, Z., Ji, J., Chen, M., Yin, L., Zhang, J., and Pu, Y. (2020). Benzene Exposure Induces Gut Microbiota Dysbiosis and Metabolic Disorder in Mice. Sci. Total Environ., 705.","DOI":"10.1016\/j.scitotenv.2019.135879"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.1223813","article-title":"Host-Gut Microbiota Metabolic Interactions","volume":"336","author":"Nicholson","year":"2012","journal-title":"Science"},{"key":"ref_66","unstructured":"Burtis, C.A., Bruns, D.E., and Sawyer, B.G. (2016). Tietz Fundamentos de Qu\u00edmica Cl\u00ednica e Diagn\u00f3stico Molecular, Elsevier. [7th ed.]."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrgentox.2016.11.002","article-title":"Biomonitoring of Gasoline Station Attendants Exposed to Benzene: Effect of Gender","volume":"813","author":"Moro","year":"2017","journal-title":"Mutat. Res.\u2014Genet. Toxicol. Environ. Mutagen."},{"key":"ref_68","first-page":"1","article-title":"Hematological and Hepatic Alterations in Nonsmoking Residents Exposed to Benzene Following a Flaring Incident at the British Petroleum Plant in Texas City","volume":"13","author":"Andrea","year":"2014","journal-title":"Environ. Health"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.jalz.2017.01.008","article-title":"Dysregulation of Lipids in Alzheimer\u2019s Disease and Their Role as Potential Biomarkers","volume":"13","author":"Wong","year":"2017","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.molmed.2018.10.009","article-title":"Ceramides as Novel Disease Biomarkers","volume":"2019","author":"Kurz","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrc.2017.96","article-title":"Sphingolipid Metabolism in Cancer Signalling and Therapy","volume":"18","author":"Ogretmen","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.3748\/wjg.v25.i24.3009","article-title":"Biomarkers and Subtypes of Deranged Lipid Metabolism in Nonalcoholic Fatty Liver Disease","volume":"25","author":"Mato","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbacli.2017.03.002","article-title":"The Plasma Lipidome in Acute Myeloid Leukemia at Diagnosis in Relation to Clinical Disease Features","volume":"7","author":"Pabst","year":"2017","journal-title":"BBA Clin."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0891-5849(91)90063-9","article-title":"Potential Role of Free Radicals in Benzene-Induced Myelotoxicity and Leukemia","volume":"11","author":"Subrahmanyam","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0162-3109(89)90029-5","article-title":"Prevention of Benzene-Induced Myelotoxicity and Prostaglandin Synthesis in Bone Marrow of Mice by Inhibitors of Prostaglandin H Synthase","volume":"18","author":"Pirozzi","year":"1989","journal-title":"Immunopharmacology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s10555-018-9754-9","article-title":"Targeting Lipid Mediators in Cancer Biology","volume":"37","author":"Sulciner","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0090-6980(98)00020-3","article-title":"Effects of Systemic Prostaglandin E 1 on Splanchnic and Peripheral Haemodynamics in Control Subjects and in Patients with Cirrhosis","volume":"55","author":"Fabbri","year":"1998","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.envint.2018.07.017","article-title":"Human Exposure to Polycyclic Aromatic Hydrocarbons: Metabolomics Perspective","volume":"119","author":"Gao","year":"2018","journal-title":"Environ. Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3748\/wjg.v6.i3.326","article-title":"Protective Effects of Prostaglandin E1 on Hepatocytes","volume":"6","author":"Liu","year":"2000","journal-title":"World J. Gastroenterol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1096\/fasebj.10.12.8903509","article-title":"Sphingolipid Metabolism and Cell Growth Regulation","volume":"10","author":"Spiegel","year":"1996","journal-title":"FASEB J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fonc.2021.632623","article-title":"Reactive Oxygen Species Rewires Metabolic Activity in Acute Myeloid Leukemia","volume":"11","author":"Robinson","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/hon.2313","article-title":"SERUM Metabolomics of Acute Lymphoblastic Leukaemia and Acute Myeloid Leukaemia for Probing Biomarker Molecules","volume":"35","author":"Musharraf","year":"2016","journal-title":"Hematol. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.intimp.2018.01.032","article-title":"Oleamide Suppresses Inflammatory Responses in LPS-Induced RAW264.7 Murine Macrophages and Alleviates Paw Edema in a Carrageenan-Induced Inflammatory Rat Model","volume":"56","author":"Moon","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Naumoska, K., Jug, U., Metli\u010dar, V., and Vovk, I. (2020). Oleamide, a Bioactive Compound, Unwittingly Introduced into the Human Body through Some Plastic Food\/Beverages and Medicine Containers. Foods, 9.","DOI":"10.3390\/foods9050549"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2165\/00129785-200202020-00002","article-title":"Metabolic Enzyme Polymorphisms and Susceptibility to Acute Leukemia in Adults","volume":"2","author":"Morgan","year":"2002","journal-title":"Am. J. Pharmacogenomics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1124\/mol.64.3.550","article-title":"Aspartate Aminotransferase Generates Proagonists of the Aryl Hydrocarbon Receptor","volume":"64","author":"Bittinger","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_87","unstructured":"Cummings, J.R., and Sakata, T. (1995). Physiological and Clinical Aspects of Short-Chain Fatty Acids, Cambridge University Press."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.ijheh.2011.11.001","article-title":"Increased Serum Levels of Advanced Oxidation Protein Products and Glycation End Products in Subjects Exposed to Low-Dose Benzene","volume":"215","author":"Spatari","year":"2012","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1042\/BJ20101695","article-title":"Molecular Targets of Oxidative Stress","volume":"434","author":"Avery","year":"2011","journal-title":"Biochem. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1093\/carcin\/bgab089","article-title":"Metabolome-Wide Association Study of Occupational Exposure to Benzene","volume":"42","author":"Rothman","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.154999","article-title":"Plasma Metabolomics Study Reveals the Critical Metabolic Signatures for Benzene-Induced Hematotoxicity","volume":"7","author":"Guo","year":"2022","journal-title":"JCI Insight"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Sun, R., Cao, M., Zhang, J., Yang, W., Wei, H., Meng, X., and Yin, L. (2016). Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid \u03b2 -Oxidation in Male C3H\/He Mice. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13111068"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/tox.22939","article-title":"l-Carnitine protects against 1,4-benzoquinone-induced apoptosisand DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells","volume":"35","author":"Sun","year":"2020","journal-title":"Environ. Toxicol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/10\/978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:22Z","timestamp":1760144122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/10\/978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,16]]},"references-count":93,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["metabo12100978"],"URL":"https:\/\/doi.org\/10.3390\/metabo12100978","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,16]]}}}