Abstract 3938: Localized synchrotron radiation affects serum cytokine levels and modulates gene expression in irradiated mouse skin and in skin distant from the irradiated site
Authors: Forrester Helen B. , Ivashkevich Alesia , Stevenson Andrew W. , Hall Christopher J. , Lobachevsky Pavel , Sprung Carl N. , Martin Olga A. 
Published: May 2015

Synchrotron radiation has great potential to improve cancer radiotherapy, a major cancer treatment received by about 50% cancer patients annually. A new synchrotron-based modality, microbeam radiotherapy (MRT), has shown promise for cancer treatment. MRT utilizes high intensity X-rays collimated to planar microbeams 25 μm-wide and with 200 μm period. MRT effectively ablates tumours but causes less damage to normal tissues compared to conventional broadbeam (BB) radiotherapy techniques. Little is known about the mechanisms underlying this remarkable result.

We initiated a study of systemic (“abscopal”, “distant bystander”) effects1,2 of MRT and BB irradiation in C57BL/6J mice. Skin areas (2x2 and 8x8 mm) were irradiated with 10 or 40 Gy, and blood and skin samples were collected at 24 and 96 hours post-irradiation. Serum levels of pro-inflammatory cytokines known to be induced by radiation or to mediate the bystander effect, were measured. In parallel, gene expression was measured in irradiated and non-irradiated skin using real time PCR.

Statistically significant changes were identified for known radiation responsive genes in both targeted and non-targeted dermal tissue after both BB and MRT treatments. Down-regulation of some genes in distant skin that were up-regulated at the site of irradiation were identified in an apparent contrasting response between these two sets of tissues. Also, the expression for some genes showed differences between MRT and BB-treated mice. MRT-specific bystander responses were also observed in distant tissue, including gene expression of TP53 for which the protein product has a fundamental role in cell fate. Levels of various cytokines in the serum were also altered in response to both BB and MRT. In some cases, the cytokine response was different for MRT compared to BB-treated samples which could potentially explain the benefits of MRT. These results advance the understanding of the biological responses to synchrotron-generated radiation and provide a potential mechanism for MRT.

References

1. Sprung, CN, Ivashkevich, A, Forrester, HB, Redon, CE, Georgakilas, AG, Martin, OA. Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects (Cancer Letters 2013, e-pub).

2. Siva, S, MacManus, MP, Martin, RF, Martin, OA. Abscopal effects of radiation therapy: a clinical review for the radiobiologist (Cancer Letters 2013, e-pub).

Acknowledgements

This work was supported by the NHMRC grant 10275598 and by the Victorian Government's Operational Infrastructure Support Program. We thank the Australian Synchrotron for use of the IMBL and facilities.

Citation Format: Helen B. Forrester, Alesia Ivashkevich, Andrew W. Stevenson, Christopher J. Hall, Pavel Lobachevsky, Carl N. Sprung, Olga A. Martin. Localized synchrotron radiation affects serum cytokine levels and modulates gene expression in irradiated mouse skin and in skin distant from the irradiated site. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3938. doi:10.1158/1538-7445.AM2014-3938