Increased mitochondrial DNA copy number in occupations associated with low-dose benzene exposure.

Michele Carugno, Angela Cecilia Pesatori, Laura Dioni, Mirjam Hoxha, Valentina Bollati, Benedetta Albetti, Hyang Min Byun, Matteo Bonzini, Silvia Fustinoni, Pierluigi Cocco, Giannina Satta, Mariagrazia Zucca, Domenico Franco Merlo, Massimo Cipolla, Pier Alberto Bertazzi, Andrea Baccarelli

Research output: Contribution to journalArticle

Abstract

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. 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. 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). 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). Blood MtDNAcn was increased in persons exposed to low benzene levels, potentially reflecting mitochondrial DNA damage and dysfunction.

Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalEnvironmental Health Perspectives
Volume120
Issue number2
DOIs
Publication statusPublished - Feb 2012

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

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    Carugno, M., Pesatori, A. C., Dioni, L., Hoxha, M., Bollati, V., Albetti, B., Byun, H. M., Bonzini, M., Fustinoni, S., Cocco, P., Satta, G., Zucca, M., Merlo, D. F., Cipolla, M., Bertazzi, P. A., & Baccarelli, A. (2012). Increased mitochondrial DNA copy number in occupations associated with low-dose benzene exposure. Environmental Health Perspectives, 120(2), 210-215. https://doi.org/10.1289/ehp.1103979