Recent studies with electron and proton beams have shown that irradiation at dose rates above 40 Gy/s can be as effective in inhibiting tumor growth as irradiation at the conventional dose currently used (typically 1 Gy/min) but much less toxic to healthy tissues. This phenomenon is known as the “FLASH effect”. This effect is considered one of the most important discoveries in the recent history of radiobiology due to its potential to improve the therapeutic window between tumor control and normal tissue toxicity. Recent studies show that the biological mechanisms of the FLASH effect are linked to differential tissue oxygenation. However, the exact mechanisms of the cellular biological effects of FLASH irradiations are not completely clear and some are even contradictory.
The objective of this project is a molecular characterization of the FLASH effect on a model system perfectly controlled in vitro. FLASH irradiations of cancer cells and healthy cells will be compared to conventional dose rate irradiations using electrons and carbon ions in the two associated laboratories. The differential effect will be related to the oxygenation condition of the cells, REDOX/mitochondrial metabolism and general changes in cellular metabolism.