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Impact of Ultra-High-Dose-Rate Irradiation on DNA: Single-Strand Breaks and Base Damage
Yucheng Wang1, Yan Zhang1, Chenyang Huang1
1Sino-French Institute of Nuclear Engineering and Technology, Sun Yat-sen University, Zhuhai 519082, China.
International Journal of Molecular Sciences
|March 13, 2025
Summary
Ultra-high-dose-rate (UHDR) irradiation significantly reduces DNA damage, including single-strand breaks (SSBs) and base damage, compared to conventional-dose-rate (CONV) irradiation. This finding is crucial for understanding the FLASH effect in radiobiology.
Area of Science:
- Radiation Biology
- Molecular Biology
- Biophysics
Background:
- Understanding DNA damage mechanisms is key to elucidating the radiobiological FLASH effect.
- Ultra-high-dose-rate (UHDR) irradiation presents unique biological outcomes compared to conventional-dose-rate (CONV) irradiation.
Purpose of the Study:
- To quantitatively compare DNA damage, specifically single-strand breaks (SSBs) and base damage, induced by UHDR and CONV irradiation.
- To investigate the influence of plasmid DNA concentration on DNA damage under different irradiation rates.
- To analyze the role of specific enzymes (Nth and Fpg) in quantifying base damage.
Main Methods:
- Irradiation of pBR322 plasmid DNA using an electron FLASH beam at UHDR and CONV.
- Quantification of DNA double-strand breaks (DSBs) and SSBs using gel electrophoresis.
- Enzymatic analysis with Nth and Fpg to assess base damage.
- Evaluation of DNA damage at varying plasmid concentrations.
Main Results:
- UHDR irradiation resulted in lower induction rates for SSBs (21.7 ± 0.4 ×10-3 SSB/Gy/molecule) compared to CONV (25.8 ± 0.3 ×10-3 SSB/Gy/molecule).
- Enzymatic analysis showed reduced base damage induction rates under UHDR (43.3 ± 2.0 ×10-3 SSB/Gy/molecule) versus CONV (58.4 ± 4.5 ×10-3 SSB/Gy/molecule).
- UHDR irradiation consistently reduced SSBs and base damage across different plasmid concentrations, though concentration itself influenced the absolute damage levels.
Conclusions:
- UHDR irradiation demonstrably reduces DNA SSBs and base damage compared to CONV irradiation.
- The protective effect of UHDR on DNA damage is observed across various plasmid concentrations.
- These findings contribute to understanding the protective mechanisms of the FLASH effect in radiobiology.
Keywords:
FLASH effectbase damageplasmid concentrationsingle-strand breakultra-high dose rate radiationMore Related Videos
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