Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status. (March 2014)

• Record Type: Journal Article
• Authors: Strigari, Lidia; Mancuso, Mariateresa; Ubertini, Valentina; Soriani, Antonella; Giardullo, Paola; Benassi, Marcello; D'Alessio, Daniela; Leonardi, Simona; Soddu, Silvia; Bossi, Gianluca
• Is Part Of: International journal of radiation biology. Volume 90:Number 3(2014:Mar.)
• Page Start: 248
• Page End: 255
• Publication Date: 2014-03
• Subjects: Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2014.874608
• Languages: English
• ISSNs: 0955-3002

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: This study investigates whether the abscopal effect induced by radiation-therapy (RT) is able to sterilize non-irradiated tumour cells through bystander signals.</p> <p> <italic>Material and methods</italic>: 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<sup>3</sup>, 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.</p> <p> <italic>Results</italic>: 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.</p> <p> <italic>Conclusions</italic>: We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells.</p> </abstract>