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One of the most intriguing and still pending questions in radiobiology is to understand whether and how natural environmental background radiation has shaped Life over millions of years of evolution on Earth. Deep Underground Laboratories (DULs) represent the ideal below-background exposure facilities where to address such a question. Among the few worldwide DULs, INFN-Laboratorio Nazionale del Gran Sasso (LNGS) is one of the largest in terms of size and infrastructure. Designed and built to host neutrino and dark matter experiments, since the 1990 s the LNGS has been one of the first DULs to systematically host radiobiology experiments. Here we present the DISCOVER22 (DNA Damage and Immune System Cooperation in VEry low Radiation environment 2022) experiment recently started at LNGS. DISCOVER22 aims at investigating how the low radiation background modulates the Immune System (IS) response in in vitro and in vivo models. Underground radiobiology experiments are particularly complex and tricky to design and perform. In these studies, the accurate characterization of exposure scenarios is mandatory, but a challenging aspect is to understand how the very few ionizing tracks in the ultra-Low Radiation Environment (LRE) interact with the living matter in space and time in order to trigger different biological responses. In this Perspective, we describe these challenges and how we address them through a microdosimetric and a radiobiological approaches. We aim at linking physical microdosimetric measurements and the corresponding biological radiation responses by using radiation biophysical models that could shed light on many as yet unresolved questions.

Radiobiological studies conducted in Deep Underground Laboratories allow to improve the knowledge of the biological effects induced by ionizing radiation at low doses/dose rates. At the Gran Sasso National Laboratory of the Italian Institute of Nuclear Physics we can study the possible differences in behavior between parallel biological systems, one maintained in a Reference-Radiation Environment (RRE, external) and the other maintained in an extremely Low-Radiation Environment (LRE, underground), in the absence of pressure changes, the RRE and LRE laboratories being at the same altitude. For these investigations, it is mandatory to evaluate the dose rate values at RRE and LRE. The aim of our work is to provide a comprehensive dosimetric analysis for external and underground laboratories. Measurements of the different low Linear Energy Transfer (LET) components at RRE and LRE were performed using different detectors. Gamma dose rates were 31 nSv/h at RRE and 27 nSv/h at LRE respectively. The muon dose rate was 47 nSv/h at RRE and negligible at LRE (less than pGy/h). Dosimetric measurements were also carried out to characterize the devices used to modulate the gamma dose rate, namely, a gamma source irradiator (to increase the dose rate by about 90 nSv/h) and shields (of iron at LRE and lead at RRE). Using the iron shield at LRE a dose reduction factor of about 20, compared to the RRE, was obtained for the low LET components; inside the lead shield at RRE the gamma component was negligible compared to the muonic component. Radon activity concentrations were approximately of 20 Bq/m3 at both LRE and RRE. The intrinsic contribution of radioactivity in the experimental set up was of 0.25 nGy/h, as evaluated with a GEANT4-simulation, using as input the measured activity concentrations. GEANT4 simulations were also performed to calculate the neutron dose rate at RRE, yielding a value of 1.4 nGy/h, much larger than that at LRE (which is less than pGy/h). In conclusion, RRE and LRE are currently characterized and equipped to perform radiobiological studies aimed at understanding the involvement of the different low LET components in determining the response of biological systems.