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

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

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
JournalInternational Journal of Oncology
Volume44
Issue number4
Pages (from-to)1073-83
Number of pages11
ISSN1019-6439
DOIs
Publication statusPublished - Apr-2014
Externally publishedYes

Keywords

  • Cell Cycle/genetics
  • DNA Breaks, Double-Stranded/radiation effects
  • DNA Damage/radiation effects
  • DNA Repair/genetics
  • Histones/genetics
  • Humans
  • Inflammation/genetics
  • Male
  • Prostatic Neoplasms/radiotherapy
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated
  • Signal Transduction/immunology

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