Experimental mouse studies are important to gain a comprehensive, quantitative and mechanistic understanding of the biological factors that modify individual risk of radiation-induced health effects, including age at exposure, dose, dose rate, organ/tissue specificity and genetic factors. In this study, neonatal Ptch1+/– mice bred on CD1 and C57Bl/6 background received whole-body irradiation at postnatal day 2. This time point represents a critical phase in the development of the eye lens, cerebellum and dentate gyrus (DG), when they are also particularly susceptible to radiation effects. Irradiation was performed with g rays (60Co) at doses of 0.5, 1 and 2 Gy, delivered at 0.3 Gy/min or 0.063 Gy/min. Wild-type and mutant mice were monitored for survival, lens opacity, medulloblastoma (MB) and neurogenesis defects. We identified an inverse genetic background-driven relationship between the radiosensitivity to induction of lens opacity and MB and that to neurogenesis deficit in Ptch1+/– mutants. In fact, high incidence of radiation-induced cataract and MB were observed in Ptch1+/–/CD1 mutants that instead showed no consequence of radiation exposure on neurogenesis. On the contrary, no induction of radiogenic cataract and MB was reported in Ptch1+/–/C57Bl/6 mice that were instead susceptible to induction of neurogenesis defects. Compared to Ptch1+/–/CD1, the cerebellum of Ptch1+/–/C57Bl/6 mice showed increased radiosensitivity to apoptosis, suggesting that differences in processing radiation-induced DNA damage may underlie the opposite strain-related radiosensitivity to cancer and non-cancer pathologies. Altogether, our results showed lack of dose-rate-related effects and marked influence of genetic background on the radiosensitivity of Ptch1+/– mice, supporting a major contribution of individual sensitivity to radiation risk in the population.
Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/– Mice
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I. De Stefano, S. Leonardi, A. Casciati, E. Pasquali, P. Giardullo, F. Antonelli, F. Novelli, G. Babini, M. Tanori, B. Tanno, A. Saran, M. Mancuso, S. Pazzaglia; Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/– Mice. Radiat Res 2021; doi: https://doi.org/10.1667/RADE-20-00247.1
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