Abstract
Background and purpose
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.
Materials and 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 10 weeks 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.
Conclusion
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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Radiotherapy and OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2004; 58: 1268-1279
- Intensity-modulated radiotherapy in the treatment of lung cancer.Clin Oncol (Royal College of Radiologists (Great Britain)). 2012; 24: 508-520
- Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research.Int J Radiat Oncol Biol Phys. 2006; 66: 1281-1293
- Dose-dependent induction of transforming growth factor beta (TGF-beta) in the lung tissue of fibrosis-prone mice after thoracic irradiation.Int J Radiat Oncol Biol Phys. 2000; 47: 1033-1042
- The bronchiolar epithelium as a prominent source of pro-inflammatory cytokines after lung irradiation.Int J Radiat Oncol Biol Phys. 2005; 61: 1482-1492
- Increased expression of pro-inflammatory cytokines as a cause of lung toxicity after combined treatment with gemcitabine and thoracic irradiation.Radiother Oncol. 2004; 72: 231-241
- Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems.Int J Radiat Oncol Biol Phys. 1995; 31: 1187-1203
- Playing the end game: DNA double-strand break repair pathway choice.Mol Cell. 2012; 47: 497-510
- Ionizing-radiation induced DNA double-strand breaks: a direct and indirect lighting up.Radiother Oncol. 2013; 108: 362-369
- A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining.J Clin Investig. 2009; 119: 91-98
- PRKDC mutations in a SCID patient with profound neurological abnormalities.J Clin Investig. 2013; 123: 2969-2980
- Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer.Nat Rev Mol Cell Biol. 2008; 9: 759-769
- Atm haploinsufficiency results in increased sensitivity to sublethal doses of ionizing radiation in mice.Nat Genet. 1999; 21: 359-360
- Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries.J Natl Cancer Inst. 2001; 93: 121-127
- Hereditary cancer predisposition syndromes.J Clin Oncol. 2005; 23: 276-292
- DNA repair alterations in children with pediatric malignancies: novel opportunities to identify patients at risk for high-grade toxicities.Int J Radiat Oncol Biol Phys. 2010; 78: 359-369
- Discordance between phosphorylation and recruitment of 53BP1 in response to DNA double-strand breaks.Cell Cycle (Georgetown, Tex.). 2012; 11: 1432-1444
- Functional dosimetric metrics for predicting radiation-induced lung injury in non-small cell lung cancer patients treated with chemoradiotherapy.Radiat Oncol (London, England). 2012; 7: 69
- Accumulation of DNA damage in complex normal tissues after protracted low-dose radiation.DNA Repair. 2012; 11: 823-832
- Repair kinetics in mouse lung after multiple X-ray fractions per day.Int J Radiat Biol. 1988; 54: 429-443
- Do variations in mast cell hyperplasia account for differences in radiation-induced lung injury among different mouse strains, rats and nonhuman primates?.Radiat Res. 2013; 180: 216-221
- Gene expression profiling distinguishes radiation-induced fibrosing alveolitis from alveolitis in mice.Radiat Res. 2010; 173: 512-521
- DNA repair in the context of chromatin: new molecular insights by the nanoscale detection of DNA repair complexes using transmission electron microscopy.DNA Repair. 2011; 10: 427-437
- Beyond repair foci: DNA double-strand break repair in euchromatic and heterochromatic compartments analyzed by transmission electron microscopy.PLoS ONE. 2012; 7: e38165
Article info
Publication history
Published online: April 21, 2014
Accepted:
March 18,
2014
Received in revised form:
January 10,
2014
Received:
October 24,
2013
Identification
Copyright
© 2014 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
