Carugno, MichelePesatori, Angela CeciliaDioni, LauraHoxha, MirjamBollati, ValentinaAlbetti, BenedettaBonzini, MatteoFustinoni, SilviaCocco, PierluigiSatta, GianninaZucca, MariagraziaMerlo, Domenico FrancoCipolla, MassimoBertazzi, Pier AlbertoByun, Hyang-MinBaccarelli, Andrea2012-04-122011Carugno, Michele, Angela Cecilia Pesatori, Laura Dioni, Mirjam Hoxha, Valentina Bollati, Benedetta Albetti, Hyang-Min Byun, et al. 2011. Increased mitochondrial DNA copy number in occupations associated with low-dose benzene exposure. Environmental Health Perspectives 120(2): 210-215.0091-6765http://nrs.harvard.edu/urn-3:HUL.InstRepos:8564479Background: 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. 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. 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 (> 100 times lower than the Occupational Safety and Health Administration/European Union standards) and 178 referents from three Italian cities (Genoa, Milan, Cagliari). 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 < 0.001). Using methylation data available for the Milan participants, we found that mtDNAcn was associated with LINE-1 hypomethylation (–2.41%; p = 0.007) and p15 hypermethylation (+15.95%, p = 0.008). Conclusions: Blood MtDNAcn was increased in persons exposed to low benzene levels, potentially reflecting mitochondrial DNA damage and dysfunction.en-USbenzenebiomarkerslow exposuresmethylationmitochondrial DNA copy numberJournal Article2012-04-1210.1289/ehp.1103979