Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 174-184 |
| Number of pages | 11 |
| Journal | Environmental and Molecular Mutagenesis |
| Volume | 60 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 2019 |
Funding
Grant sponsor: National Institute of General Medical Sciences; Grant number: P30GM103338. Grant sponsor: Nuclear R&D Program of the Ministry of Sciences and Technology of Korea; Grant number: M20504050002-05A0705-00211. Grant sponsor: University of Montana; Grant number: UGP Small Grant. This work was supported by the Nuclear R&D Program of the Ministry of Sciences and Technology of Korea (M20504050002-05A0705–00211), Institutional Development Award (IDeA) from the National Institute of General Medical Sciences, NIH (P30GM103338), and UGP funding (Small grant) from the University of Montana. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
| Funders | Funder number |
|---|---|
| M20504050002-05A0705–00211 | |
| University of Montana | |
| P30GM103338 | |
Keywords
- LINE-1
- global DNA hypomethylation
- radiation
- radiation-induced genomic instability
- radiographers
