Abscopal Gene Expression in Response to Synchrotron Radiation Indicates a Role for Immunological and DNA Damage Response Genes.

Forrester, Helen B; Lobachevsky, Pavel N; Stevenson, Andrew W; Hall, Christopher J; Martin, Olga A.; Sprung, Carl N (2020). Abscopal Gene Expression in Response to Synchrotron Radiation Indicates a Role for Immunological and DNA Damage Response Genes. Radiation research, 194(6), pp. 678-687. Radiation Research Society 10.1667/RADE-19-00014.1

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Abscopal effects are an important aspect of targeted radiation therapy due to their implication in normal tissue toxicity from chronic inflammatory responses and mutagenesis. Gene expression can be used to determine abscopal effects at the molecular level. Synchrotron microbeam radiation therapy utilizing high-intensity X rays collimated into planar microbeams is a promising cancer treatment due to its reported ability to ablate tumors with less damage to normal tissues compared to conventional broadbeam radiation therapy techniques. The low scatter of synchrotron radiation enables microbeams to be delivered to tissue effectively, and is also advantageous for out-of-field studies because there is minimal interference from scatter. Mouse legs were irradiated at a dose rate of 49 Gy/s and skin samples in the out-of-field areas were collected. The out-of-field skin showed an increase in Tnf expression and a decrease in Mdm2 expression, genes associated with inflammation and DNA damage. These expression effects from microbeam exposure were similar to those found with broadbeam exposure. In immune-deficient Ccl2 knockout mice, we identified a different gene expression profile which showed an early increase in Mdm2, Tgfb1, Tnf and Ccl22 expression in out-of-field skin that was not observed in the immune-proficient mice. Our results suggest that the innate immune system is involved in out-of-field tissue responses and alterations in the immune response may not eliminate abscopal effects, but could change them.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy
UniBE Contributor:	Martin, Olga Alexeevna
Subjects:	600 Technology > 610 Medicine & health
ISSN:	0033-7587
Publisher:	Radiation Research Society
Language:	English
Submitter:	Benoît Zuber
Date Deposited:	11 Dec 2020 07:32
Last Modified:	05 Dec 2022 15:42
Publisher DOI:	10.1667/RADE-19-00014.1
PubMed ID:	32991732
URI:	https://boris.unibe.ch/id/eprint/149415