title: Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity.
abstract: OBJECTIVE
  Intensity-modulated radiation therapy for thoracic malignancies increases the exposure of healthy lung tissue to low-dose radiation. The biological impact of repetitive low-dose radiation on the radiosensitive lung is unclear.
  
  
  METHODS
  In the present study, using mouse strains with different genetic DNA repair capacities, we monitored the extent of DNA damage in lung parenchyma after 2, 4, 6, 8, and 10weeks of daily low-dose 100-mGy radiation.
  
  
  RESULTS
  Using 53BP1 as a marker for double-strand breaks, we observed DNA damage accumulation during fractionated low-dose radiation with increasing cumulative doses. The amount of radiation-induced 53BP1 varied significantly between bronchiolar and alveolar epithelial cells, suggesting that different cell populations in the lung parenchyma had varying vulnerabilities to ionizing radiation. The genetic background of DNA repair determined the extent of cumulative low-dose radiation damage. Moreover, increased DNA damage during fractionated low-dose radiation affected replication, and apoptosis in the lung parenchyma, which may influence overall lung function.
  
  
  CONCLUSIONS
  Collectively, our results suggest that low, yet damaging, doses of radiation increase the risk of toxicity to normal lung tissue and the probability of developing secondary malignancies.
authors.affiliation: Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Flockerzi
authors.affiliation: Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schanz
authors.affiliation: Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany. Electronic address: claudia.ruebe@uks.eu.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Rübe
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005819:Genetic Markers; D006801:Humans; D008168:Lung / Q000528:radiation effects*; D055370:Lung Injury / Q000209:etiology*; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000235:genetics* / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1
keywords: 53BP1 foci; DNA double-strand breaks; Low-dose radiation; Lung tissue; Non-homologous end-joining; Normal tissue toxicity