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Hu, A.* ; Qiu, R.* ; Li, W.B. ; Zhou, W.* ; Wu, Z.* ; Zhang, H.* ; Li, J.*

Radical recombination and antioxidants: A hypothesis on the FLASH effect mechanism.

Int. J. Radiat. Biol., DOI: 10.1080/09553002.2022.2110307 (2022)
Postprint DOI PMC
Open Access Green
Purpose: FLASH (ultra-high dose rate) radiotherapy spares normal tissue while keeping tumor control. However, the mechanism of the FLASH effect remains unclear and may have consequences beyond the irradiated area. Materials and methods: We reanalyze the available results of ultra-high-dose-rate-related experiments to find out the key points of the mechanism of the FLASH effect. Then, we present a hypothesis on the mechanism of the FLASH effect: FLASH beams generate a high transient concentration of peroxyl radicals leading to a high fraction of radical recombination, which results in less oxidation damage to normal tissue. For the cells containing higher concentrations of antioxidants, the fractions of radical recombination are smaller because the antioxidants compete to react with peroxyl radicals. Therefore the damages by different dose rate beams differ slightly in this condition. Since some tumors contain a higher level of antioxidants, this may be the reason for the loss of the protective effect in tumors irradiated by FLASH beams. The high concentration of antioxidants in tumors results in slight radiolytic oxygen consumption, and consequently the protective effect observed in in vitro experiment cannot be observed in in vivo experiment. To quantitatively elaborate our hypothesis, a kinetic model is implemented to simulate the reactions induced by irradiation. Two parameters are defined to abstractly study the factors affecting the reaction, such as dose rate, antioxidants, total dose and reaction rate constants. Results and conclusions: We find that the explanation of the difference between in vivo and in vitro experiments is crucial to understanding the mechanism of the FLASH effect. Our hypothesis agrees with the results of related experiments. Based on the kinetic model, the effects of these factors on the FLASH effect are quantitatively investigated.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Peroxyl Radical ; Antioxidant ; Radical Recombination ; Radiation ; Flash Radiotherapy
ISSN (print) / ISBN 0955-3002
e-ISSN 1362-3095
Zeitschrift International Journal of Radiation Biology
Verlag Informa Healthcare
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Medicine (IRM)
Förderungen Tsinghua University Initiative Scientific Research Program
National Natural Science Foundation of China (NSFC)