High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood. (July 2013)

• Record Type: Journal Article
• Authors: Manning, Grainne; Kabacik, Sylwia; Finnon, Paul; Bouffler, Simon; Badie, Christophe
• Is Part Of: International journal of radiation biology. Volume 89:Number 7(2013:Jul.)
• Page Start: 512
• Page End: 522
• Publication Date: 2013-07
• Subjects: Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2013.769694
• Languages: English
• ISSNs: 0955-3002

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: Modifications of gene expression following ionizing radiation (IR) exposure of cells in vitro and in vivo are well documented. However, little is known about the dose-responses of transcriptionally responsive genes, especially at low doses. In this study, we investigated these dose-responses and assessed inter-individual variability.</p> <p> <italic>Materials and methods:</italic> High dose (0.5–4 Gy) and low dose (5–100 mGy) gene expression responses at 2 h and 24 h using 13 biomarkers transcriptionally regulated through the DNA damage response by the tumor suppressor p53 were investigated. Inter-individual variation was also examined.</p> <p> <italic>Results</italic>: High dose-response curves were best constructed using a polynomial fit while the low dose-response curves used a linear fit with linear R<sup>2</sup> values of 0.841–0.985. Individual variation was evident in the high and low dose ranges. The <italic>FDXR, DDB2</italic> high dose gene combination produced a mean dose estimate of 0.7 Gy for 1 Gy irradiated 'unknown' samples (95% CIs of 0.3–1.1 Gy) and 1.4 Gy for 2 Gy exposure (95% CIs of 0.6–2.1 Gy). The <italic>FDXR, DDB2, CCNG1</italic> low dose gene combination estimated 98 mGy (95% CIs of 27–169 mGy) for 100 mGy exposure.</p> <p> <italic>Conclusions</italic>: These findings identify genes that fulfill some of the requirements of a good exposure biomarker even at low doses, such as sensitivity, reproducibility and simple proportionality with dose.</p> </abstract>