{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:32:50Z","timestamp":1791999170178,"version":"4.4.0"},"reference-count":55,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2265,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Benzene is an established leukemogen at high exposure levels. Although low-level benzene exposure is widespread and may induce oxidative damage, no mechanistic biomarkers are available to detect biological dysfunction at low doses.<\/jats:p>\n                  <jats:p>Objectives: Our goals were to determine in a large multicenter cross-sectional study whether low-level benzene is associated with increased blood mitochondrial DNA copy number (mtDNAcn, a biological oxidative response to mitochondrial DNA damage and dysfunction) and to explore potential links between mtDNAcn and leukemia-related epigenetic markers.<\/jats:p>\n                  <jats:p>Methods: We measured blood relative mtDNAcn by real-time polymerase chain reaction in 341 individuals selected from various occupational groups with low-level benzene exposures (&amp;gt; 100 times lower than the Occupational Safety and Health Administration\/European Union standards) and 178 referents from three Italian cities (Genoa, Milan, Cagliari).<\/jats:p>\n                  <jats:p>Results: In each city, benzene-exposed participants showed higher mtDNAcn than referents: mtDNAcn was 0.90 relative units in Genoa bus drivers and 0.75 in referents (p = 0.019); 0.90 in Milan gas station attendants, 1.10 in police officers, and 0.75 in referents (p-trend = 0.008); 1.63 in Cagliari petrochemical plant workers, 1.25 in referents close to the plant, and 0.90 in referents farther from the plant (p-trend = 0.046). Using covariate-adjusted regression models, we estimated that an interquartile range increase in personal airborne benzene was associated with percent increases in mtDNAcn equal to 10.5% in Genoa (p = 0.014), 8.2% (p = 0.008) in Milan, 7.5% in Cagliari (p = 0.22), and 10.3% in all cities combined (p &amp;lt; 0.001). Using methylation data available for the Milan participants, we found that mtDNAcn was associated with LINE-1 hypomethylation (\u20132.41%; p = 0.007) and p15 hypermethylation (+15.95%, p = 0.008).<\/jats:p>\n                  <jats:p>Conclusions: Blood MtDNAcn was increased in persons exposed to low benzene levels, potentially reflecting mitochondrial DNA damage and dysfunction.<\/jats:p>","DOI":"10.1289\/ehp.1103979","type":"journal-article","created":{"date-parts":[[2011,10,17]],"date-time":"2011-10-17T11:11:17Z","timestamp":1318849877000},"page":"210-215","source":"Crossref","is-referenced-by-count":102,"title":["Increased Mitochondrial DNA Copy Number in Occupations Associated with Low-Dose Benzene Exposure"],"prefix":"10.1021","volume":"120","author":[{"given":"Michele","family":"Carugno","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Cecilia","family":"Pesatori","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda \u2013 Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dioni","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Hoxha","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bollati","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Albetti","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyang-Min","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Bonzini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Insubria, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Fustinoni","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda \u2013 Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Cocco","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Technologies, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giannina","family":"Satta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Technologies, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Zucca","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Technologies, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico Franco","family":"Merlo","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics and Clinical Trials and Environmental Chemistry Units, Department of Cancer Epidemiology and Prevention, National Cancer Research Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Cipolla","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics and Clinical Trials and Environmental Chemistry Units, Department of Cancer Epidemiology and Prevention, National Cancer Research Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Alberto","family":"Bertazzi","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Universit\u00e0 degli Studi di Milano, Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda \u2013 Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Baccarelli","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, 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