High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood

Grainne Manning, Sylwia Kabacik, Paul Finnon, Simon Bouffler, Christophe Badie*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    74 Citations (Scopus)

    Abstract

    Purpose: 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. Materials and methods: 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. Results: High dose-response curves were best constructed using a polynomial fit while the low dose-response curves used a linear fit with linear R2 values of 0.841-0.985. Individual variation was evident in the high and low dose ranges. The FDXR, DDB2 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 FDXR, DDB2, CCNG1 low dose gene combination estimated 98 mGy (95% CIs of 27-169 mGy) for 100 mGy exposure. Conclusions: 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.

    Original languageEnglish
    Pages (from-to)512-522
    Number of pages11
    JournalInternational Journal of Radiation Biology
    Volume89
    Issue number7
    DOIs
    Publication statusPublished - Jul 2013

    Bibliographical note

    Funding Information:
    Financial support was provided by the National Institute for Health Research Centre for Research in Public Health Protection at the Health Protection Agency.

    Copyright:
    Copyright 2014 Elsevier B.V., All rights reserved.

    Keywords

    • Biological dosimetry
    • Biomarkers
    • Dose-response
    • Gene expression
    • Ionising radiation
    • Peripheral blood lymphocytes

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