title: Oncogenic radiation abscopal effects in vivo: interrogating mouse skin.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Casaccia Research Centre, Rome, Italy. mariateresa.mancuso@enea.it
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Mancuso
authors.forename: Simona
authors.initials: S
authors.lastname: Leonardi
authors.forename: Paola
authors.initials: P
authors.lastname: Giardullo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pasquali
authors.forename: Mirella
authors.initials: M
authors.lastname: Tanori
authors.forename: Ilaria
authors.initials: I
authors.lastname: De Stefano
authors.forename: Arianna
authors.initials: A
authors.lastname: Casciati
authors.forename: Christian C
authors.initials: CC
authors.lastname: Naus
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
mesh_terms: D000818:Animals; D017209:Apoptosis; D002280:Basal Cell Carcinoma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology; D003433:Crosses, Genetic; D004249:DNA Damage; D017629:Gap Junctions / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011835:Radiation Protection / Q000379:methods; D011836:Radiation Tolerance / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018031:Connexin 43; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface