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Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin.
- Source :
-
International Journal of Radiation Oncology, Biology, Physics . Aug2013, Vol. 86 Issue 5, p993-999. 7p. - Publication Year :
- 2013
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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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03603016
- Volume :
- 86
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- International Journal of Radiation Oncology, Biology, Physics
- Publication Type :
- Academic Journal
- Accession number :
- 89139560
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2013.04.040