|Title||Oncogenic radiation abscopal effects in vivo: Interrogating mouse skin|
|Publication Type||Articolo su Rivista peer-reviewed|
|Year of Publication||2013|
|Authors||Mancuso, Mariateresa, Leonardi Simona, Giardullo Paola, Pasquali Emanuela, Tanori Mirella, De Stefano Ilaria, Casciati Arianna, Naus C.C., Pazzaglia Simonetta, and Saran Anna|
|Journal||International Journal of Radiation Oncology Biology Physics|
|Keywords||animal experiment, animal tissue, Animals, Apoptosis, article, Basal Cell, basal cell carcinoma, Carcinoma, cell death, Cell Surface, connexin 43, controlled study, Crosses, DNA damage, Double strand breaks, double stranded DNA break, Gap junction intercellular communications, Gap Junctions, Gene Knockdown Techniques, Genetic, immunohistochemistry, in vivo study, Mammals, Methods and materials, Mice, mouse, Mouse models, Neoplasms, nonhuman, priority journal, Radiation, Radiation effects, radiation protection, Radiation signals, Radiation Tolerance, Radiation-Induced, Receptors, signal transduction, Skin, skin carcinogenesis, Skin Neoplasms, Tissue, Tumor induction, Tumorigenesis|
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. © 2013 Elsevier Inc.
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