Global and MGMT promoter hypomethylation independently associated with genomic instability of lymphocytes in subjects exposed to high-dose polycyclic aromatic hydrocarbon
详细信息 查看全文
- 作者：Huawei Duan (1)
Zhini He (2)
Junxiang Ma (1)
Bo Zhang (2)
Zhiguo Sheng (3)
Ping Bin (1)
Juan Cheng (1)
Yong Niu (1)
Haiyan Dong (1)
Han Lin (4)
Yufei Dai (1)
Benzhan Zhu (3)
Wen Chen (2)
Yongmei Xiao (2)
Yuxin Zheng (1) - 关键词：Global methylation ; O6 ; methylguanine ; DNA methyltransferase (MGMT) ; Genomic instability ; Polycyclic aromatic hydrocarbon ; DNA adducts
- 刊名：Archives of Toxicology
- 出版年：2013
- 出版时间：November 2013
- 年：2013
- 卷：87
- 期：11
- 页码：2013-2022
- 全文大小：
- 作者单位：Huawei Duan (1)
Zhini He (2)
Junxiang Ma (1)
Bo Zhang (2)
Zhiguo Sheng (3)
Ping Bin (1)
Juan Cheng (1)
Yong Niu (1)
Haiyan Dong (1)
Han Lin (4)
Yufei Dai (1)
Benzhan Zhu (3)
Wen Chen (2)
Yongmei Xiao (2)
Yuxin Zheng (1)
1. Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing, 100050, People? Republic of China
2. Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People? Republic of China
3. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, People? Republic of China
4. Institute of Industrial Health, Anshan Steel Industrial Corporation, Anshan, 114044, People? Republic of China - ISSN：1432-0738
文摘
Global hypomethylation, gene-specific methylation, and genome instability are common events in tumorigenesis. To date, few studies have examined the aberrant DNA methylation patterns in coke oven workers, who are highly at risk of lung cancer by occupational exposure to polycyclic aromatic hydrocarbons (PAHs). We recruited 82 PAH-exposed workers and 62 unexposed controls, assessed exposure levels by urinary 1-hydroxypyrene, and measured genetic damages by comet assay, bleomycin sensitivity, and micronucleus assay. The PAHs in coke oven emissions (COE) were estimated based on toxic equivalency factors. We used bisulfite-PCR pyrosequencing to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and O6-methylguanine-DNA methyltransferase (MGMT). Further, the methylation alteration was also investigated in COE-treated human bronchial epithelial (16HBE) cells. We found there are higher levels of PAHs in COE. Among PAH-exposed workers, LINE-1 and MGMT methylation levels (with CpG site specificity) were significantly lowered. LINE-1, MGMT, and its hot CpG site-specific methylation were negatively correlated with urinary 1-hydroxypyrene levels (r?=??0.329, p?<?0.001; r?=??0.164, p?=?0.049 and r?=??0.176, p?=?0.034, respectively). In addition, LINE-1 methylation was inversely associated with comet tail moment and micronucleus frequency, and a significant increase of micronucleus in low MGMT methylation group. In vitro study revealed that treatment of COE in 16HBE cells resulted in higher production of BPDE-DNA adducts, LINE-1 hypomethylation, hypomethylation, and suppression of MGMT expression. These findings suggest hypomethylation of LINE-1 and MGMT promoter could be used as markers for PAHs exposure and merit further investigation.