LINE-1 hypomethylation is associated with radiation-induced genomic instability in industrial radiographers

Yoon Hee Cho, Yoonhee Jang, Hae Dong Woo, Yang Jee Kim, Su Young Kim, Sonja Christensen, Elizabeth Cole, Soo Yong Choi, Hai Won Chung

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)174-184
Number of pages11
JournalEnvironmental and Molecular Mutagenesis
Volume60
Issue number2
DOIs
StatePublished - Mar 2019

Keywords

  • LINE-1
  • global DNA hypomethylation
  • radiation
  • radiation-induced genomic instability
  • radiographers

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