Low-dose effects of ionizing radiations in in vitro and in vivo biological systems: A multi-scale approach study

Long-term biological effects of low-dose radiation are little known nowadays and its carcinogenic risk is estimated on the assumption that the risk remains linearly proportional to the radiation dose down to low-dose levels. However in the last 20 years this hypothesis has gradually begun to seem in contrast with a huge collection of experimental evidences, which has shown the presence of a plethora of non-linear phenomena (including hypersensitivity and induced radioresistance, adaptive response, and non-targeted phenomena like bystander effect and genomic instability) occurring after low-dose irradiation. These phenomena might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the Linear No-Threshold (LNT) model currently used for cancer risk assessment through extrapolation from existing high-dose data. Moreover only few information is available regarding the effects induced on cryopreserved cells by multi-year background radiation exposure, which might induce a radiation-damage accumulation, due to the inhibition of cellular repair mechanisms. In this framework, the multi-year EXCALIBUR (EXposure effeCts At Low doses of Ionizing radiation in Biological CultURes) experiment, funded by INFN-CNS5, has undertaken a multiscale approach investigation on the biological effects induced in in vitro and in vivo biological systems, in culture and cryopreserved conditions, as a function of radiation quality (X/gamma-rays, protons, He-4 ions of various energies) and dose, with particular emphasis on the low-dose region and non-linear phenomena, in terms of different biological endpoints.