Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

El-Saghire,Houssein; Vandevoorde,Charlot; Ost,Piet; Monsieurs,Pieter; Michaux,Arlette; De Meerleer,Gert; Baatout,Sarah; Thierens,Hubert

doi:10.3892/ijo.2014.2260

Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

Authors:
- Houssein El-Saghire
- Charlot Vandevoorde
- Piet Ost
- Pieter Monsieurs
- Arlette Michaux
- Gert De Meerleer
- Sarah Baatout
- Hubert Thierens
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Affiliations: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium, Department of Basic Medical Sciences, Ghent University, Gent, Belgium, Department of Radiation Oncology, Ghent University Hospital, Gent, Belgium
Published online on: January 17, 2014 https://doi.org/10.3892/ijo.2014.2260
Pages: 1073-1083
Copyright: © El-Saghire et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18-24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation.

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