title: Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status.
abstract: OBJECTIVE
  This study investigates whether the abscopal effect induced by radiation-therapy (RT) is able to sterilize non-irradiated tumour cells through bystander signals.
  
  
  METHODS
  Wild-type (wt)-p53 or p53-null HCT116 human colon cancer cells were xenografted into both flanks of athymic female nude mice. When tumours reached a volume of 0.2 cm(3), irradiation was performed, under strict dose monitoring, with a dedicated mobile accelerator designed for intra-Operative-RT (IORT). A dose of 10 or 20 Gy (IR groups), delivered by a 10 MeV electron beam, was delivered to a tumour established in one side flank, leaving the other non-irradiated (NIR groups). A subset of mice were sacrificed early on to carry out short-term molecular analyses.
  
  
  RESULTS
  All directly-irradiated tumours, showed a dose-dependent delayed and reduced regrowth, independent of the p53 status. Importantly, a significant effect on tumour-growth inhibition was also demonstrated in NIR wt-p53 tumours in the 20 Gy-irradiation group, with a moderate effect also evident after 10 Gy-irradiation. In contrast, no significant difference was observed in the NIR p53-null tumours, independent of the dose delivered. Molecular analyses indicate that p53-dependent signals might be responsible for the abscopal effect in our model system, via a pro-apoptotic pathway.
  
  
  CONCLUSIONS
  We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells.
authors.affiliation: Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute , Rome.
authors.forename: Lidia
authors.initials: L
authors.lastname: Strigari
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Mancuso
authors.forename: Valentina
authors.initials: V
authors.lastname: Ubertini
authors.forename: Antonella
authors.initials: A
authors.lastname: Soriani
authors.forename: Paola
authors.initials: P
authors.lastname: Giardullo
authors.forename: Marcello
authors.initials: M
authors.lastname: Benassi
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Alessio
authors.forename: Simona
authors.initials: S
authors.lastname: Leonardi
authors.forename: Silvia
authors.initials: S
authors.lastname: Soddu
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bossi
mesh_terms: D000818:Animals; D017209:Apoptosis; D024201:Bystander Effect / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D005260:Female; D005720:Gamma Rays; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D011874:Radiometry / Q000379:methods; D011878:Radiotherapy / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53