For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti-inflammatory/antioxidant agent. Their potential influence on the transcriptional response to radiation of the genes CCNG1 and PHPT1, two biomarkers of radiation exposure ex vivo, was assessed. First, both CCNG1 and PHPT1 were detected in vivo in blood samples from radiotherapy patients and as such were validated as biomarkers of exposure. Importantly, their basal expression level was slightly but significantly affected in vivo by patients' cancer condition. Moreover, lipopolysaccharide stimulation of blood irradiated ex vivo led to a significant modification of CCNG1 and PHPT1 transcriptional response in a dose-and time-dependent manner with opposite regulatory effects. Curcumin also affected CCNG1 and PHPT1 transcriptional response counteracting some of the radiation induction. No differences were observed based on sex. Dose estimations calculated using linear regression were affected by lipopolysaccharide and curcumin. In conclusion, several confounding factors tested in this study can indeed modulate the transcriptional response of CCNG1 and PHPT1 and consequently can affect radiation exposure dose estimations but not to a level which should prevent the biomarkers' use for triage purposes.
|Number of pages||12|
|Publication status||Published - 1 Jul 2018|
Bibliographical noteFunding Information:
Acknowledgments—This project received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement No. 249689 and from the OPERRA project (EC FP7) under grant agreement No. 604984. It also received financial support from the Radiation Theme of the Newcastle University, Public Health England (PHE) Health Protection Research Unit (HPRU), and the U.S. National Institutes of Health (NIH). The authors also acknowledge U.K. National Health Service (NHS) funding to the U.K. National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research (ICR).
© 2018 Lippincott Williams & Wilkins.
- biological indicators
- exposure, radiation
- radiation dose
- radiation therapy