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FLASH Irradiation Spares Lung Progenitor Cells and Limits the Incidence of Radio-induced Senescence.

Author information

Affiliations

  • 1. Institut Curie, Inserm U 1021-CNRS UMR 3347, University Paris-Saclay, PSL Research University, Centre Universitaire, Orsay, France.
      Authors
    • Fouillade C 1
    • Curras-Alonso S 1, 4
    • Quelennec E 1
    • Heinrich S 1
    • Bonnet-Boissinot S 1
    • Beddok A 1
    • Dutreix M 1
    • Favaudon V 1
    (8 authors)
  • 2. Department of Radiotherapy, Grow-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
      Authors
    • Giuranno L 2
    • Vooijs M 2
    (2 authors)
  • 3. Institut Curie, CNRS UMR 3348, University Paris-Saclay, PSL Research University, Centre Universitaire, Orsay, France.
      Authors
    • Leboucher S 3
    (1 author)
  • 4. Institut Curie, CNRS UMR 3244, PSL Research University, Paris, France.
      Authors
    • Curras-Alonso S 1, 4
    • Karakurt HU 4
    • Londoño-Vallejo A 4
    (3 authors)
  • 5. Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France.
      Authors
    • Bohec M 5
    • Baulande S 5
    (2 authors)
    • Show all (6)

ORCIDs linked to this article

Show all (10)

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 03 Dec 2019, 26(6):1497-1506
https://doi.org/10.1158/1078-0432.ccr-19-1440 PMID: 31796518 

Abstract 

Purpose

One of the main limitations to anticancer radiotherapy lies in irreversible damage to healthy tissues located within the radiation field. "FLASH" irradiation at very high dose-rate is a new treatment modality that has been reported to specifically spare normal tissue from late radiation-induced toxicity in animal models and therefore could be a promising strategy to reduce treatment toxicity.

Experimental design

Lung responses to FLASH irradiation were investigated by qPCR, single-cell RNA sequencing (sc-RNA-Seq), and histologic methods during the acute wound healing phase as well as at late stages using C57BL/6J wild-type and Terc-/- mice exposed to bilateral thorax irradiation as well as human lung cells grown in vitro.

Results

In vitro studies gave evidence of a reduced level of DNA damage and induced lethality at the advantage of FLASH. In mouse lung, sc-RNA-seq and the monitoring of proliferating cells revealed that FLASH minimized the induction of proinflammatory genes and reduced the proliferation of progenitor cells after injury. At late stages, FLASH-irradiated lungs presented less persistent DNA damage and senescent cells than after CONV exposure, suggesting a higher potential for lung regeneration with FLASH. Consistent with this hypothesis, the beneficial effect of FLASH was lost in Terc-/- mice harboring critically short telomeres and lack of telomerase activity.

Conclusions

The results suggest that, compared with conventional radiotherapy, FLASH minimizes DNA damage in normal cells, spares lung progenitor cells from excessive damage, and reduces the risk of replicative senescence.

Full text links 

Read article at publisher's site: https://doi.org/10.1158/1078-0432.ccr-19-1440

Read article for free, from open access legal sources, via Unpaywall: https://clincancerres.aacrjournals.org/content/clincanres/26/6/1497.full.pdfUnpaywall

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Funding 

Funders who supported this work.

French National Research Agency (1)

Institut Curie (3)

Marie Skøodowska-Curie (2)