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. 2022 Feb 24;14(5):1167. doi: 10.3390/cancers14051167

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Oxygen depletion hypothesis of the FLASH effect. Tumors are extremely hypoxic relative to their surrounding normal tissue, with oxygen tensions ranging from 0.3% to 4.2%. The surrounding normal tissue is more highly oxygenated (i.e., physioxia), usually between 3% and 7.4% [36]. For this reason, a more pronounced decrease in oxygen level after FLASH treatment is observed in physioxic conditions compared with tumors. This correlates with a significant decrease in radiosensitivity (or increase in radiation resistance) in normal tissues, conferring the FLASH effect. Tumors, on the other hand, show little change in radiosensitivity, leading to the absence of the FLASH effect.