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

Environ Mol Mutagen. 2019 Mar;60(2):174-184. doi: 10.1002/em.22237. Epub 2018 Nov 29.

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. © 2018 Wiley Periodicals, Inc.

Keywords: LINE-1; global DNA hypomethylation; radiation; radiation-induced genomic instability; radiographers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Damage / radiation effects*
  • DNA Methylation / genetics*
  • DNA Methylation / radiation effects
  • Female
  • Genomic Instability / radiation effects*
  • Humans
  • Long Interspersed Nucleotide Elements / radiation effects*
  • Male
  • Micronucleus Tests
  • Middle Aged
  • Occupational Exposure
  • Radiation Exposure
  • Radiography / adverse effects