Increased Mitochondrial DNA Copy Number in Occupations Associated with Low-Dose Benzene Exposure

被引：108

作者：

Carugno, Michele ^{[1
]}

Pesatori, Angela Cecilia ^{[1
,2
]}

Dioni, Laura ^{[1
]}

Hoxha, Mirjam ^{[1
]}

Bollati, Valentina ^{[1
]}

Albetti, Benedetta ^{[1
]}

Byun, Hyang-Min ^{[3
]}

Bonzini, Matteo ^{[4
]}

Fustinoni, Silvia ^{[2
]}

Cocco, Pierluigi ^{[5
]}

Satta, Giannina ^{[5
]}

Zucca, Mariagrazia ^{[5
]}

Merlo, Domenico Franco ^{[6
,7
,8
]}

Cipolla, Massimo ^{[6
,7
,8
]}

Bertazzi, Pier Alberto ^{[1
,2
]}

Baccarelli, Andrea ^{[3
]}

机构：

[1] Univ Milan, Dept Occupat & Environm Hlth, I-20122 Milan, Italy

[2] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Milan, Italy

[3] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA

[4] Univ Insubria, Dept Clin & Biol Sci, Varese, Italy

[5] Univ Cagliari, Dept Biomed Sci & Technol, Cagliari, Italy

[6] Natl Inst Canc Res, Dept Canc Epidemiol & Prevent, Epidemiol Unit, Genoa, Italy

[7] Natl Inst Canc Res, Dept Canc Epidemiol & Prevent, Biostat Unit, Genoa, Italy

[8] Natl Inst Canc Res, Dept Canc Epidemiol & Prevent, Clin Trials & Environm Chem Unit, Genoa, Italy

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 2012年 / 120卷 / 02期

关键词：

benzene; biomarkers; low exposures; methylation; mitochondrial DNA copy number; METHYLATION PATTERNS; PARTICULATE MATTER; CANCER-RISK; HYPERMETHYLATION; EPIGENETICS; METABOLITES; CARCINOGENS; DAMAGE; GENES;

D O I：

10.1289/ehp.1103979

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

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. 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 (rntDNAcn, 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.

引用

页码：210 / 215

页数：6

共 55 条

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