DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood

Helen Budworth, Antoine M. Snijders, Francesco Marchetti, Brandon Mannion, Sandhya Bhatnagar, Ely Kwoh, Yuande Tan, Shan X. Wang, William F. Blakely, Matthew A Coleman, Leif Peterson, Andrew J. Wyrobek

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS). Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06<p<0.03), of which 8 showed no overlap between unirradiated and irradiated samples (CDKN1A, FDXR, BBC3, PCNA, GADD45a, XPC, POLH and DDB2). This panel demonstrated excellent dose response discrimination (0.5 to 8 Gy) in an independent human blood ex vivo dataset, and 100% accuracy for discriminating patients who received total body radiation. Three genes of this panel (CDKN1A, FDXR and BBC3) were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ~90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

Original languageEnglish (US)
Article numbere48619
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 7 2012

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Biomarkers
DNA repair
DNA Repair
lipopolysaccharides
cell cycle
biomarkers
Cell Cycle
Repair
Blood
inflammation
Cells
Lipopolysaccharides
Radiation
Inflammation
DNA
blood
genes
exposure scenario
Genes
Gene Expression

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Budworth, H., Snijders, A. M., Marchetti, F., Mannion, B., Bhatnagar, S., Kwoh, E., ... Wyrobek, A. J. (2012). DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood. PLoS One, 7(11), [e48619]. https://doi.org/10.1371/journal.pone.0048619

DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood. / Budworth, Helen; Snijders, Antoine M.; Marchetti, Francesco; Mannion, Brandon; Bhatnagar, Sandhya; Kwoh, Ely; Tan, Yuande; Wang, Shan X.; Blakely, William F.; Coleman, Matthew A; Peterson, Leif; Wyrobek, Andrew J.

In: PLoS One, Vol. 7, No. 11, e48619, 07.11.2012.

Research output: Contribution to journalArticle

Budworth, H, Snijders, AM, Marchetti, F, Mannion, B, Bhatnagar, S, Kwoh, E, Tan, Y, Wang, SX, Blakely, WF, Coleman, MA, Peterson, L & Wyrobek, AJ 2012, 'DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood', PLoS One, vol. 7, no. 11, e48619. https://doi.org/10.1371/journal.pone.0048619
Budworth H, Snijders AM, Marchetti F, Mannion B, Bhatnagar S, Kwoh E et al. DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood. PLoS One. 2012 Nov 7;7(11). e48619. https://doi.org/10.1371/journal.pone.0048619
Budworth, Helen ; Snijders, Antoine M. ; Marchetti, Francesco ; Mannion, Brandon ; Bhatnagar, Sandhya ; Kwoh, Ely ; Tan, Yuande ; Wang, Shan X. ; Blakely, William F. ; Coleman, Matthew A ; Peterson, Leif ; Wyrobek, Andrew J. / DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood. In: PLoS One. 2012 ; Vol. 7, No. 11.
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