Oncogenic radiation abscopal effects in vivo: interrogating mouse skin.

TitleOncogenic radiation abscopal effects in vivo: interrogating mouse skin.
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2013
AuthorsMancuso, Mariateresa, Leonardi Simona, Giardullo Paola, Pasquali Emanuela, Tanori Mirella, De Stefano Ilaria, Casciati Arianna, Naus Christian C., Pazzaglia Simonetta, and Saran Anna
JournalInt J Radiat Oncol Biol Phys
Volume86
Issue5
Pagination993-9
Date Published2013 Aug 01
ISSN1879355X
KeywordsAnimals, Apoptosis, Carcinoma, Basal Cell, connexin 43, Crosses, Genetic, DNA damage, Gap Junctions, Gene Knockdown Techniques, Mice, Neoplasms, Radiation-Induced, patched receptors, Patched-1 Receptor, radiation protection, Radiation Tolerance, Receptors, Cell Surface, Skin, Skin Neoplasms
Abstract

PURPOSE: To investigate the tissue dependence in transmission of abscopal radiation signals and their oncogenic consequences in a radiosensitive mouse model and to explore the involvement of gap junction intercellular communication (GJIC) in mediating radiation tumorigenesis in off-target mouse skin.

METHODS AND MATERIALS: Patched1 heterozygous (Ptch1(+/-)) mice were irradiated at postnatal day 2 (P2) with 10 Gy of x-rays. Individual lead cylinders were used to protect the anterior two-thirds of the body, whereas the hindmost part was directly exposed to radiation. To test the role of GJICs and their major constituent connexin43 (Cx43), crosses between Ptch1(+/-) and Cx43(+/-) mice were similarly irradiated. These mouse groups were monitored for their lifetime, and skin basal cell carcinomas (BCCs) were counted and recorded. Early responses to DNA damage - Double Strand Breaks (DSBs) and apoptosis - were also evaluated in shielded and directly irradiated skin areas.

RESULTS: We report abscopal tumor induction in the shielded skin of Ptch1(+/-) mice after partial-body irradiation. Endpoints were induction of early nodular BCC-like tumors and macroscopic infiltrative BCCs. Abscopal tumorigenesis was significantly modulated by Cx43 status, namely, Cx43 reduction was associated with decreased levels of DNA damage and oncogenesis in out-of-field skin, suggesting a key role of GJIC in transmission of oncogenic radiation signals to unhit skin.

CONCLUSIONS: Our results further characterize the nature of abscopal responses and the implications they have on pathologic processes in different tissues, including their possible underlying mechanistic bases.

DOI10.1016/j.ijrobp.2013.04.040
Alternate JournalInt. J. Radiat. Oncol. Biol. Phys.
PubMed ID23755921