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

• Published in: Radiation research Vol. 197; no. 1; p. 43
• Main 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
• Format: Journal Article
• Language: English
• Published: United States 01.01.2022
• Subjects: Animals; Dose-Response Relationship, Radiation; Gamma Rays; Genetic Background; Humans; Lens, Crystalline - radiation effects; Medulloblastoma - ethnology; Mice; Mice, Inbred C57BL; Neoplasms, Radiation-Induced - etiology; Neurogenesis; Radiation Tolerance; Whole-Body Irradiation
• ISSN: 1938-5404
• DOI: 10.1667/RADE-20-00247.1

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.