Ecology

Biology

Materials science

Nuclear physics

Oxygenation

Radiochemistry

Limiting oxygen concentration

Physical chemistry

Physics

Radiosensitivity

Organic chemistry

Oxygen

Irradiation

Optics

Flash (photography)

Aqueous solution

Oxygen enhancement ratio

Radiolysis

Chemistry

Biophysics

Radiotherapy and Oncology

<h2>Abstract</h2><h3>Background and purpose</h3> Recent observations in animal models show that ultra-high dose rate ("FLASH") radiation treatment significantly reduces normal tissue toxicity maintaining an equivalent tumor control. The dependence of this "FLASH" effect on target oxygenation has led to the assumption that oxygen "depletion" could be its major driving force. <h3>Materials and Methods</h3> In a bottom-up approach <b>s</b>tarting from the chemical track evolution of 1 MeV electrons in oxygenated water simulated with the TRAX-CHEM Monte Carlo code, we determine the oxygen consumption and radiolytic reactive oxygen species production following a short radiation pulse. Based on these values, the effective dose weighted by oxygen enhancement ratio (OER) or the <i>in vitro</i> cell survival under dynamic oxygen pressure is calculated and compared to that of conventional exposures, at constant OER. <h3>Results</h3> We find an excellent agreement of our Monte Carlo predictions with the experimental value for radiolytic oxygen removal from oxygenated water. However, the application of the present model to published radiobiological experiment conditions shows that oxygen depletion can only have a negligible impact on radiosensitivity through oxygen enhancement, especially at typical experimental oxygenations where a FLASH effect has been observed. <h3>Conclusion</h3> We show that the magnitude and dependence of the "oxygen depletion" hypothesis are not consistent with the observed biological effects of FLASH irradiation. While oxygenation plays an undoubted role in mediating the FLASH effect, we conclude that state-of-the-art radiation chemistry models do not support oxygen depletion and radiation-induced transient hypoxia as the main mechanism.

May oxygen depletion explain the FLASH effect? A chemical track structure analysis