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- Title
Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1<sup>+/–</sup> Mice.
- Authors
De Stefano, I.; Leonardi, S.; Casciati, A.; Pasquali, E.; Giardullo, P.; Antonelli, F.; Novelli, F.; Babini, G.; Tanori, M.; Tanno, B.; Saran, A.; Mancusoa, M.; Pazzaglia, S.
- Abstract
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.
- Subjects
BACKGROUND radiation; DISEASE risk factors; RADIATION tolerance; DENTATE gyrus; CRYSTALLINE lens; RADIATION exposure
- Publication
Radiation Research, 2022, Vol 197, Issue 1, p43
- ISSN
0033-7587
- Publication type
Article
- DOI
10.1667/RADE-20-00247.1