Effectiveness of laser accelerated ultra high dose rate protons in DNA DSB damage induction under hypoxic conditions

Particle therapy has been regarded as an effective modality for treating tumors due to higher RBE than photons and precise dose delivery to the deep seated tumors near the critical organs offering significantly sparing of the normal tissues 1 . High LET ions have been reported to kill radioresistant and hypoxic tumor cells. The large footprint, installation and operational costs of the current particle therapy facilities pose a challenge towards the widespread accessibility of particle therapy. High-power lasers have successfully demonstrated the generation of ion beams, which have been proposed as a route towards reducing the overall footprint and costs of future hadrontherapy facilities. In view of this potential future application a detailed radiobiology of the interaction of laser accelerated ions beams with biological systems is highly warranted. Radiation induced reactive oxygen species (ROS) lead to cellular damage through the induction of an array of lesions including DNA base damage, single strand beaks and double strand breaks and induce apoptosis and necrotic cell death. Under hypoxia, the proliferation rate of tumor cells beats the vasculature formation rate leading to the development of oxygen deficient zones within the tumor. Such hypoxic zones leads to reduced radiotherapy response owing to a decrease in ROS that are required to produce lethal DNA damage. In this paper we aim to study the effectiveness of laser-accelerated protons in the induction of DNA DSB damage in hypoxic human cells through a comparison to 225 kVp X-rays and cyclotron accelerated protons.