Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation in vivo, we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated (ARG1, BCL2L1) or downregulated (MYC) several fold in vivo. These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes CD40, OAS2, and CXCR1 whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity.

Biomedical Research Centre University Hospital Hradec Králové Hradec Králové Czechia

Cancer Mechanisms and Biomarkers Group Centre for Radiation Chemical and Environmental Hazards Radiation Effects Department Public Health England Oxfordshire UK

Clinic of Oncology and Radiotherapy University Hospital Hradec Králové Hradec Králové Czechia

Department of Radiobiology Faculty of Military Health Sciences in Hradec Králové University of Defence Brno Czechia

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Transcriptional Inflammatory Signature in Healthy Donors and Different Radiotherapy Cancer Patients

In Vivo Validation of Alternative FDXR Transcripts in Human Blood in Response to Ionizing Radiation

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood