title: Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients.
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.
authors.affiliation: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium.
authors.forename: Houssein
authors.initials: H
authors.lastname: El-Saghire
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Gent, Belgium.
authors.forename: Charlot
authors.initials: C
authors.lastname: Vandevoorde
authors.affiliation: Department of Radiation Oncology, Ghent University Hospital, Gent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.affiliation: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Monsieurs
authors.affiliation: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium.
authors.forename: Arlette
authors.initials: A
authors.lastname: Michaux
authors.affiliation: Department of Radiation Oncology, Ghent University Hospital, Gent, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Meerleer
authors.affiliation: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Gent, Belgium.
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated; D015398:Signal Transduction / Q000276:immunology* / Q000528:radiation effects
chemical_list: C468783:H2AX protein, human; D006657:Histones