Increased mitochondrial DNA copy number in occupations associated with low-dose benzene exposure.
Increased mitochondrial DNA copy number in occupations associated with low-dose benzene exposure.
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DOI：
10.1289/ehp.1103979
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发表时间：
2012-02
影响因子：
10.4
通讯作者：
Baccarelli A
中科院分区：
文献类型：
--
作者：
Carugno M;Pesatori AC;Dioni L;Hoxha M;Bollati V;Albetti B;Byun HM;Bonzini M;Fustinoni S;Cocco P;Satta G;Zucca M;Merlo DF;Cipolla M;Bertazzi PA;Baccarelli A
背景：苯在高暴露水平下是一种已确定的白血病原。虽然低水平的苯暴露是广泛的，并可能诱导氧化损伤，没有机制的生物标志物可用于检测低剂量的生物功能障碍。目的：我们的目标是在一项大型多中心横断面研究中确定低水平苯是否与血液线粒体DNA拷贝数（mtDNA，对线粒体DNA损伤和功能障碍的生物氧化反应）增加相关，并探索mtDNA和白血病相关表观遗传标记之间的潜在联系。研究方法：我们通过实时聚合酶链反应测量了341名来自不同职业人群的低水平苯暴露（比职业安全与健康管理局/欧盟标准低100倍以上）的个体和178名来自意大利三个城市（热那亚，米兰，卡利亚里）的参考者的血液相对mtDNA。结果如下：在每个城市中，苯暴露的参与者显示出比参照物更高的mtDNA：热那亚公交车司机的mtDNA相对单位为0.90，参照物为0.75（p = 0.019）;米兰加油站服务员为0.90，警察为1.10，参照为0.75（p趋势= 0.008）;卡利亚里石化厂工人中为1.63，工厂附近的参照物中为1.25，远离工厂的参照物中为0.90（p趋势= 0.046）。使用协变量调整回归模型，我们估计个人空气中苯的四分位数范围增加与mtDNAcn增加百分比相关，在热那亚为10.5%（p = 0.014），米兰为8.2%（p = 0.008），卡利亚里为7.5%（p = 0.22），所有城市合并为10.3%（p < 0.001）。使用米兰参与者的甲基化数据，我们发现mtDNAcn与LINE-1低甲基化（-2.41%，p = 0.007）和p15高甲基化（+15.95%，p = 0.008）相关。结论：血液MtDNAn增加暴露于低苯水平的人，可能反映线粒体DNA损伤和功能障碍。
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 (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.
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影响因子：
3.6
作者：
Baccarelli A;Bollati V
通讯作者：
Bollati V
影响因子：
4.1
作者：
Han, D;Williams, E;Cadenas, E
通讯作者：
Cadenas, E
影响因子：
11.2
作者：
Bollati, Valentina;Baccarelli, Andrea;Yang, Allen S.
通讯作者：
Yang, Allen S.
DOI：
10.1164/rccm.200807-1097oc
发表时间：
2009-04-01
影响因子：
24.7
作者：
Baccarelli, Andrea;Wright, Robert O.;Schwartz, Joel
通讯作者：
Schwartz, Joel
影响因子：
11.4
作者：
Deneberg, S.;Grovdal, M.;Lehmann, S.
通讯作者：
Lehmann, S.