LINE-1 hypomethylation is associated with radiation-induced genomic instability in industrial radiographers
LINE-1 hypomethylation is associated with radiation-induced genomic instability in industrial radiographers
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DOI：
10.1002/em.22237
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发表时间：
2019-03-01
影响因子：
2.8
通讯作者：
Chung, Hai Won
中科院分区：
文献类型：
--
作者：
Cho, Yoon Hee;Jang, Yoonhee;Chung, Hai Won
整体DNA低甲基化被认为是与基因组不稳定性相关的癌症风险的潜在生物标志物，基因组不稳定性是辐射诱发癌症的一个重要因素。然而，辐射暴露、DNA甲基化变化和致癌作用之间的关系尚不清楚。本研究的目的是：（1）检查低水平职业辐射暴露是否诱导基因组DNA低甲基化;（2）确定工业放射技师的辐射暴露、基因组DNA低甲基化和辐射诱导的基因组不稳定性（RIGI）之间的关系。使用LINE-1焦磷酸测序法和发光甲基化测定法测量了40名放射技师和28名对照者血液DNA中的基因组DNA甲基化水平。此外，进行微核-着丝粒测定以测量染色体1和4的非整倍性作为延迟RIGI的标记。放射技师的基因组DNA甲基化水平显著低于对照组。LINE-1低甲基化与放射技师近1年、近3年或总累积辐射剂量无显著相关性;但LINE-1低甲基化与无近3年暴露数据的累积辐射剂量显著相关（D3剂量，r =-0.39，P < 0.05）。此外，LINE-1低甲基化是D3剂量的非整倍体频率的显著贡献者（F（2，34）= 13.85，P < 0.001），其中解释了非整倍体频率的总共45%的方差。我们的研究结果提供了有关放射技师低剂量职业辐射暴露的延迟效应及其与LINE-1低甲基化的相关性的提示性证据;然而，需要使用更多受试者进行额外的研究以充分了解基因组DNA低甲基化与RIGI之间的关系。Environ.摩尔变异体60：174-184，2019. (c)2018 Wiley Periodicals，Inc.
Global DNA hypomethylation is proposed as a potential biomarker for cancer risk associated with genomic instability, which is an important factor in radiation-induced cancer. However, the associations among radiation exposure, changes in DNA methylation, and carcinogenesis are unclear. The aims of this study were (1) to examine whether low-level occupational radiation exposure induces genomic DNA hypomethylation; and (2) to determine the relationships between radiation exposure, genomic DNA hypomethylation and radiation-induced genomic instability (RIGI) in industrial radiographers. Genomic DNA methylation levels were measured in blood DNA from 40 radiographers and 28 controls using the LINE-1 pyrosequencing assay and the luminometric methylation assay. Further, the micronucleus-centromere assay was performed to measure aneuploidy of chromosomes 1 and 4 as a marker of delayed RIGI. Genomic DNA methylation levels were significantly lower in radiographers than those in controls. LINE-1 hypomethylation was not significantly correlated with recent 1-year, recent 3-year, or total cumulative radiation doses in radiographers; however, LINE-1 hypomethylation significantly correlated with the cumulative radiation dose without recent 3-year exposure data (D3dose, r = -0.39, P < 0.05). In addition, LINE-1 hypomethylation was a significant contributor to aneuploidy frequency by D3dose (F (2, 34) = 13.85, P < 0.001), in which a total of 45% of the variance in aneuploidy frequency was explained. Our results provide suggestive evidence regarding the delayed effects of low-dose occupational radiation exposure in radiographers and its association with LINE-1 hypomethylation; however, additional studies using more subjects are needed to fully understand the relationship between genomic DNA hypomethylation and RIGI. Environ. Mol. Mutagen. 60: 174-184, 2019. (c) 2018 Wiley Periodicals, Inc.