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Published on: January 7, 2019
Biological effects in normal cells exposed to FLASH dose rate protons
Manuela Buonanno1, Veljko Grilj1, David J Brenner1
1Radiological Research Accelerator Facility (RARAF), New York, United States.
FLASH proton radiotherapy shows promise for reducing normal tissue toxicity. High dose rate proton irradiation mitigated long-term detrimental effects in lung fibroblasts, suggesting potential for improved cancer treatment outcomes.
Area of Science:
- Radiation Oncology
- Biophysics
- Cell Biology
Background:
- Radiotherapy efficacy is often limited by toxicity to healthy tissues surrounding tumors.
- FLASH radiotherapy, using dose rates >40 Gy/s, shows reduced normal tissue side effects with photons/electrons.
- FLASH effects of protons remain under-investigated due to facility limitations.
Purpose of the Study:
- To investigate FLASH proton effects on normal human lung fibroblasts.
- To assess acute and long-term biological responses to varying proton dose rates.
Main Methods:
- Human lung fibroblasts (IMR90) were irradiated with 4.5 MeV protons at dose rates from 0.05 to 1000 Gy/s.
- Evaluated endpoints included clonogenic cell survival, γH2AX foci, premature senescence (β-gal), and TGFβ expression.
Main Results:
- Proton dose rate did not affect cell survival.
- γH2AX foci formation saturated at high dose rates (>10 Gy at 1000 Gy/s).
- Increased dose and dose rate enhanced senescence and TGFβ1 expression in cell progeny.
Conclusions:
- Proton dose rate minimally impacted acute effects in lung fibroblasts.
- Dose rate significantly influenced long-term biological responses in vitro.
- FLASH proton irradiation mitigated delayed detrimental effects compared to conventional dose rates.
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