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Oncogenic radiation abscopal effects in vivo: interrogating mouse skin.

TitoloOncogenic radiation abscopal effects in vivo: interrogating mouse skin.
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2013
AutoriMancuso, Mariateresa, Leonardi Simona, Giardullo Paola, Pasquali Emanuela, Tanori Mirella, De Stefano Ilaria, Casciati Arianna, Naus Christian C., Pazzaglia Simonetta, and Saran Anna
RivistaInt J Radiat Oncol Biol Phys
Data di pubblicazione2013 Aug 01
Parole chiaveAnimals, 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

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.

Alternate JournalInt. J. Radiat. Oncol. Biol. Phys.
Citation Key5062
PubMed ID23755921