Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/- Mice

TitleContribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/- Mice
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2022
AuthorsDe Stefano, Ilaria, Leonardi Simona, Casciati Arianna, Pasquali Emanuela, Giardullo Paola, Antonelli Francesca, Novelli Flavia, Babini G., Tanori Mirella, Tanno Barbara, Saran A., Mancuso M., Pazzaglia Simonetta, and Consortium LDLensRad
JournalRadiation research

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 γ 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. ©2022 by Radiation Research Society. All rights of reproduction in any form reserved.


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