Speaker
Dr
Simona Leonardi
(ENEA CR Casaccia, Rome, Italy)
Description
The aim of this work was to investigate the dose and spatial dependence of abscopal radiation effects occurring in vivo in the mouse, along with their tumorigenic potential in radiosensitive Patched1 heterozygous (Ptc1+/-) central nervous system (CNS). Ptc1+/- mice, carrying a germ-line heterozygous inactivating mutation in the Ptc1 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 bystander protocols. In partial-body irradiation experiments, the animals’ head was fully protected by suitable lead cylinders while the remainder of the body was exposed to X-rays. Apoptotic cell death was measured in directly irradiated and shielded cerebellum at different time points after irradiation, while tumor development was monitored in lifetime groups. The same end-points were measured in mice irradiated with 3 or 10 Gy of X rays using different shielding geometries. We show a clear dose dependence of in vivo transmission of radiation signals to non-target mouse CNS. While dose-dependent cell-death was observed in off-target cerebellum for all doses and shielding conditions tested, a conspicuous lack of bystander response for CNS tumorigenesis occurred at the lowest dose of 1 Gy in body-exposed/head-shielded animals. The shielding geometry could also significantly modulate tumorigenesis as a function of dose. Our study shows a clear interplay of radiation dose and exposed tissue volume in abscopal effects occurring in mouse CNS under conditions relevant to humans. The results may help understanding the mechanisms of long-range radiation signaling in harmful effects, including carcinogenesis, occurring in off-target tissues.
Primary author
Dr
Mariateresa Mancuso
(ENEA CR Casaccia)
Co-authors
Dr
Anna Saran
(ENEA CR Casaccia, Rome, Italy)
Dr
Arianna Casciati
(ENEA CR Casaccia, Rome, Italy)
Dr
Emanuela Pasquali
(Gugliemo Marconi University, Rome, Italy)
Dr
Ilaria De Stefano
(Gugliemo Marconi University, Rome, Italy)
Dr
Mirella Tanori
(ENEA CR Casaccia, Rome, Italy)
Dr
Paola Giardullo
(Gugliemo Marconi University, Rome, Italy)
Dr
Simona Leonardi
(ENEA CR Casaccia, Rome, Italy)
Dr
Simonetta Pazzaglia
(ENEA CR Casaccia, Rome, Italy)
