Peter Vaupel (Germany)
University of Freiburg Radiation OncologyAuthor Of 1 Presentation
A RADIATION BIOLOGICAL ANALYSIS OF THE POSSIBLE MECHANISM FOR THE OXYGEN EFFECT IN FLASH
Abstract
Background and Aims
There are at least two very plausible radiobiological mechanisms for the oxygen effect in FLASH: 1) Directly, by depletion of oxygen at critical molecular sites directly changing the amount of radiation damage; 2) Indirectly by modifying physiologically mediated changes in response to radiation damage via alterations in repair and/or cell signaling. The overwhelming amount of radiation-induced damage that ultimately leads to cell death occurs in DNA. Oxygen directly radiosensitizes by reaction with transient intermediates in the DNA. Hypoxia also can modify damage from ionizing radiation inducing changes in signaling and in repair mechanisms that differ between tumors and normal tissues.
Methods
Radiobiological Principles
Results
Based on studies with cells there are lesions in DNA that have lifetimes as long as 10-5 or 10-6 seconds. The pertinent distance from which oxygen can diffuse to the sensitive site is 100-1000 nm assuming the diffusion rate of oxygen is 2.1x10-5 cm2/sec within the environment around the DNA. Therefore a technique is needed that can follow the oxygen level with spatial resolution of the nucleus and a time scale of 10-5 seconds or faster. No currently available method can do this directly. This might be done if detailed spatial distribution of oxygen inside the cell is known and the rate of oxygen depletion in a nucleus can be determined by a combination of direct measurements of oxygen, genomic alterations, and appropriate calculations.
Conclusions
Using established principles of radiation biology it should be feasible to rigorously determine if and how oxygen is involved in the mechanism of FLASH.