Increased circulating cell-free DNA levels and mtDNA fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation

Environ Mol Mutagen. 2015 Apr;56(3):293-300. doi: 10.1002/em.21917. Epub 2014 Oct 18.

Abstract

Circulating cell-free DNA (ccf-DNA) and mtDNA (ccf-mtDNA) have often been used as indicators of cell death and tissue damage in acute and chronic disorders, but little is known about changes in ccf-DNA and ccf-mtDNA concentrations following radiation exposure. The aim of the study was to investigate the impact of chronic low-dose radiation exposure on serum ccf-DNA levels and ccf-mtDNA fragments (mtDNA-79 and mtDNA-230) of interventional cardiologists working in high-volume cardiac catheterization laboratory to assess their possible role as useful radiation biomarkers. We enrolled 50 interventional cardiologists (26 males; age = 48.4 ± 10 years) and 50 age- and gender-matched unexposed controls (27 males; age = 47.6 ± 8.3 years). Quant-iT™ dsDNA High-Sensitivity assay was used to measure circulating ccf-DNA isolated from serum samples. Quantitative analysis of mtDNA fragments was performed by real-time PCR. No significant relationships were found between ccf-DNA and ccf-mtDNA, and age, gender, smoking, or other clinical parameters. Ccf-DNA levels (44.2 ± 31.1 vs. 30.6 ± 19.2 ng/ml, P = 0.013), ccf-mtDNA-79 (2.6 ± 2.1 vs. 1.1 ± 0.8, P < 0.01), and ccf-mtDNA-230 copies (2.0 ± 1.8 vs. 1.04 ± 0.9, P = 0.02) were significantly higher in interventional cardiologists compared with the non-exposed group. In a subset (n = 15) of interventional cardiologists with a reliable reconstruction of cumulative professional exposure (59.7 ± 48.4 mSv; range: 1.4-182 mS), ccf-DNA (53.2 ± 41.3 vs. 36.4 ± 22.9 and 32.2 ± 20.5, P = 0.08), mtDNA-79 (2.4 ± 2.1 vs. 2.03 ± 1.7 and 1.09 ± 0.82, P = 0.05), and mtDNA-230 (2.0 ± 2.2 vs. 1.5 ± 1.4 and 1.04 ± 0.9, P = 0.09) tended to be significantly increased in high-exposure subjects compared with both low-exposure interventional cardiologists and controls. Our results provide evidence for a possible role of circulating DNA as a relevant biomarker of cellular damage induced by exposure to chronic low-dose radiation.

Keywords: biomarker; circulating cell-free DNA; circulating cell-free mtDNA; interventional cardiologists; radiation exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cardiology Service, Hospital
  • DNA / blood*
  • DNA / genetics
  • DNA, Mitochondrial / blood*
  • DNA, Mitochondrial / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Occupational Exposure / adverse effects
  • Occupational Exposure / analysis*
  • Physicians
  • Polymerase Chain Reaction
  • Radiation Dosage
  • Radiation, Ionizing

Substances

  • Biomarkers
  • DNA, Mitochondrial
  • DNA