AUTHOR=Lobachevsky Pavel , Forrester Helen B. , Ivashkevich Alesia , Mason Joel , Stevenson Andrew W. , Hall Chris J. , Sprung Carl N. , Djonov Valentin G. , Martin Olga A. 

TITLE=Synchrotron X-Ray Radiation-Induced Bystander Effect: An Impact of the Scattered Radiation, Distance From the Irradiated Site and p53 Cell Status

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.685598

DOI=10.3389/fonc.2021.685598

ISSN=2234-943X

ABSTRACT=Cancer radiotherapy is based on the dogma that radiation kills targeted cells. The radiation-induced bystander effect (RIBE), by which the neighbours of irradiated cells can also be damaged, challenges this dogma. RIBE is now a well-established consequence of ionizing radiation and is manifested as increased genomic abnormalities and loss of viability of the ‘naïve’ cells. Therefore, RIBE represents a risk factor in radiotherapy that needs to be considered, including for treatment with novel radiotherapy modalities, such as synchrotron-generated microbeam radiotherapy (MRT). Here, we quantitatively assessed the contribution of scattered synchrotron radiation to the observed RIBE, manifested as DNA damage in cultured human colon cancer cells, for both a collimated MRT beam and a broad beam (homogeneous) control.  We report that scattered radiation substantially contributes to DNA damage accumulation in bystander cells, and that the cells exposed to the low-dose scatter generate unrepairable DNA damage, possibly due to an ongoing exchange of bystander signalling. We found a more pronounced bystander response following irradiation with broad beam compared to MRT. For p53-null cells, we describe an overall reduced response to low-dose irradiation, but not for RIBE. Our findings provide new information for optimization and planning of cancer MRT regimens.