Dose and spatial effects in long-distance radiation signaling in vivo: Implications for abscopal tumorigenesis

Mariateresa Mancuso, Paola Giardullo, Simona Leonardi, Emanuela Pasquali, Arianna Casciati, Ilaria De Stefano, Mirella Tanori, Simonetta Pazzaglia, Anna Saran

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Purpose: To investigate the dose and spatial dependence of abscopal radiation effects occurring in vivo in the mouse, along with their tumorigenic potential in the central nervous system (CNS) of a radiosensitive mouse model. Methods and Materials: Patched1 (Ptch1)+/-mice, carrying a germ-line heterozygous inactivating mutation in the Ptch1 gene and uniquely susceptible to radiation damage in neonatal cerebellum, were exposed directly to ionizing radiation (1, 2, or 3 Gy of x-rays) or treated in a variety of partial-body irradiation protocols, in which the animals' head was fully protected by suitable lead cylinders while the rest of the body was exposed to x-rays in full or in part. Apoptotic cell death was measured in directly irradiated and shielded cerebellum shortly after irradiation, and tumor development was monitored in lifetime groups. The same endpoints were measured using different shielding geometries in mice irradiated with 3 or 10 Gy of x-rays. Results: Although dose-dependent cell death was observed in off-target cerebellum for all doses and shielding conditions tested, a conspicuous lack of abscopal response for CNS tumorigenesis was evident at the lowest dose of 1 Gy. By changing the amount of exposed body volume, the shielding geometry could also significantly modulate tumorigenesis depending on dose. Conclusions: We conclude that interplay between radiation dose and exposed tissue volume plays a critical role in nontargeted effects occurring in mouse CNS under conditions relevant to humans. These findings may help understanding the mechanisms of long-range radiation signaling in harmful effects, including carcinogenesis, occurring in off-target tissues. © 2013 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)813 - 819
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number3
Publication statusPublished - 1 Mar 2013
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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