New challenges in high-energy particle radiobiology

Abstract

Densely ionizing radiation has always been a main topic in radiobiology. In fact, a-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.Biological effects of densely ionizing radiation have been studied since the beginning of radiobiology. As a matter of fact, a-particles deliver the main contribution to the background radiation dose on Earth, owing to inhalation of the indoor radon.1 Neutrons have also been extensively studied because of protection of workers in nuclear power plants; use of fast neutrons in radiotherapy; and of the exposure of the survivors of the atomic bomb in Hiroshima and Nagasaki, where a neutron component was added to g-rays. Bacq and Alexander 2 already elegantly described the radiobiology of a-particles and neutrons in their 1955 seminal book.More recently, radiobiology research has focused on highenergy protons and heavy ions, mostly for two reasons: charged particle therapy (CPT) in oncology and radiation protection in manned space missions. In both cases, charged particles at energies .100 MeV n 21 are involved. The characteristic depth-dose distribution with the sharp Bragg peak at the end of the range can be exploited for killing tumours; on the other hand, densely ionizing radiation can effectively delay tissue morbidity. Notwithstanding the many differences in exposure conditions, CPT and space radiation protection share several research topics, including individual sensitivity, non-targeted effects, late stochastic effects and so forth.3 Research in these fields requires large high-energy accelerators and is often performed by the same research groups with a common interest in particle radiobiology. Research is rapidly moving forward owing to the diffusion of CPT centres in the USA, Europe, and Asia 4 and to the growing interest in manned space exploration, now a priority for all space agencies, 5 but wi...

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