| Autor: |
HeThese authors contributed equally to this work., Zhini, Duan, Huawei, Zhang, Biao, Li, Miao, Chen, Liping, Zhang, Bo, Zhu, Xiaonian, Gao, Chen, Li, Jie, Zhang, Xiao, Zhang, Jingmaio, Wang, Shan, Zeng, Xiaowen, Li, Daochuan, Xing, Xiumei, Zhang, Zhengbao, Ma, Lu, Bai, Qing, Liu, Caixia, Xiao, Yongmei, Zheng, Yuxin, Chen, Wen |
| Zdroj: |
Toxicology Research; 2015, Vol. 4 Issue: 4 p848-857, 10p |
| Abstrakt: |
Previous studies have shown an etiologic link between exposure to polycyclic aromatic hydrocarbons (PAHs) and lung cancer development. While the tumor suppressor gene RASSF1ais mostly silenced by DNA methylation in various tumors, it is unclear whether aberrant methylation of RASSF1ais involved in the process of PAH-induced biological consequences. To address this issue, 69 coke-oven workers (exposure group) and 46 steel rolling workers (control group) were recruited in this study. Bisulfite sequencing (BSP) was performed to examine the methylation status of RASSF1apromoter in peripheral blood lymphocytes (PBLs) from PAH-exposed and control workers. The DNA fragment examined lies across −282 bp to +638 bp from the transcription start site, containing 966 bp and 87 CpG sites across the RASSF1apromoter. Of the 87 CpG sites we analyzed, 5 were significantly hypermethylated in the PAH-exposed workers compared to the control (2.5% vs.0%, P< 0.001). We defined these 5 CpG sites as “Hot CpG sites”. The levels of methylation from Hot CpG sites were positively correlated with the concentration of urinary 1-OHP (β= 0.98, P= 0.001) and the frequency of cytokinesis-block micronucleus (CBMN) (β= 1.29, P= 0.019) in PBLs, indicating that PAH exposure induced CpG site-specific hypermethylation of RASSF1awas associated with the levels of internal exposure and the degree of DNA damage. Moreover, the Hot CpG site hypermethylation and the corresponding down-regulation of RASSF1aexpression were also found in COE (coke-oven emission)-treated human primary lymphocytes and HBE cells. Taken together, these observations revealed that RASSF1aHot CpG site hypermethylation could be a promising biomarker for the PAH exposure and DNA damage. |
| Databáze: |
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