ArticleRadiation oncology (London, England)2022
Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications.
Article in Radiation oncology (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 15 citations in OpenAlex.
- Development and validation of cost-effective multi-sample hypoxia chambers for proton ultra-high dose rate organoid irradiations.Clinical and translational radiation oncology · 2025Article
- Ultra‑high dose rate (FLASH) treatment: A novel radiotherapy modality (Review).Molecular and clinical oncology · 2025Review
- Influence factor and mechanism of FLASH effect.Frontiers in oncology · 2025Review
- Oxygen Effect on 0-30 eV Electron Damage to DNA Under Different Hydration Levels: Base and Clustered Lesions, Strand Breaks and Crosslinks.Molecules (Basel, Switzerland) · 2024Article
- Combining a noble gas with radiotherapy: glutamate receptor antagonist xenon may act as a radiosensitizer in glioblastoma.Radiation oncology (London, England) · 2024Article
- Emerging technologies for cancer therapy using accelerated particles.Progress in particle and nuclear physics · 2023Article
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23 authors at 5 institutions in 5 countries.
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Abstract
backgroundThere is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 10 MATERIALS AND
methodsWe used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells.
resultsOxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers.
conclusionWe demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.
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