Abstract
Accidental exposure to ionizing radiation can be unforeseen, rapid, and devastating. The detonation of a radiological device leading to such an exposure can be detrimental to the exposed population. The radiation-induced damage may manifest as acute effects that can be detected clinically or may be more subtle effects that can lead to long-term radiation-induced abnormalities. Accurate identification of the individuals exposed to radiation is challenging. The availability of a rapid and effective screening test that could be used as a biomarker of radiation exposure detection is mandatory. We tested the suitability of alterations in gene expression to serve as a biomarker of human radiation exposure. To develop a useful gene expression biomonitor, however, gene expression changes occurring in response to irradiation in vivo must be measured directly. Patients undergoing radiation therapy provide a suitable test population for this purpose. We examined the expression of CC3, MADH7, and SEC PRO in blood samples of these patients before and after radiotherapy to measure the in vivo response. The gene expression after ionizing radiation treatment varied among different patients, suggesting the complexity of the response. The expression of the SEC PRO gene was repressed in most of the patients. The MADH7 gene was found to be upregulated in most of the subjects and could serve as a molecular marker of radiation exposure.
References
Goffman T. Lack of strategic insight: the “dirty bomb” effort. Am J Disaster Med. 2009;4(3):181–3.
Wolbarst AB, Wiley AL Jr, Nemhauser JB, Christensen DM, Hendee WR. Medical response to a major radiologic emergency: a primer for medical and public health practitioners. Radiology. 2010;254(3):660–77. doi:10.1148/radiol.09090330.
Chaudhry MA. Biomarkers for human radiation exposure. J Biomed Sci. 2008;15(5):557–63. doi:10.1007/s11373-008-9253-z.
Chaudhry MA. Bystander effect: biological endpoints and microarray analysis. Mutat Res. 2006;597(1–2):98–112. doi:10.1016/j.mrfmmm.2005.04.023.
Rodrigues AS, Oliveira NG, Gil OM, Leonard A, Rueff J. Use of cytogenetic indicators in radiobiology. Radiat Prot Dosim. 2005;115(1–4):455–60.
Leonard A, Rueff J, Gerber GB, Leonard ED. Usefulness and limits of biological dosimetry based on cytogenetic methods. Radiat Prot Dosim. 2005;115(1–4):448–54.
Pinto MM, Santos NF, Amaral A. Current status of biodosimetry based on standard cytogenetic methods. Radiat Environ Biophys. 2010;49(4):567–81. doi:10.1007/s00411-010-0311-3.
Chaudhry MA. Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2′-deoxyguanine glycosylase. Int J Cancer. 2006;118(3):633–42. doi:10.1002/ijc.21392.
Chaudhry MA. Analysis of gene expression in normal and cancer cells exposed to gamma-radiation. J Biomed Biotechnol. 2008;2008:541678. doi:10.1155/2008/541678.
Amundson SA, Do KT, Shahab S, Bittner M, Meltzer P, Trent J, et al. Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation. Radiat Res. 2000;154(3):342–6.
Templin T, Paul S, Amundson SA, Young EF, Barker CA, Wolden SL, et al. Radiation-induced micro-RNA expression changes in peripheral blood cells of radiotherapy patients. Int J Radiat Oncol Biol Phys. 2011;80(2):549–57. doi:10.1016/j.ijrobp.2010.12.061.
Chaudhry MA. Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2′-deoxyguanine glycosylase. Int J Cancer. 2006;118(3):633–42.
Williams BB, Dong R, Nicolalde RJ, Matthews TP, Gladstone DJ, Demidenko E, et al. Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation. Int J Radiat Biol. 2011;87(8):766–75. doi:10.3109/09553002.2011.583316.
Wood T, Lewis BJ, McDermott K, Bennett LG, Avarmaa K, Corcoran EC, et al. Use of a dual-labelled oligonucleotide as a DNA dosemeter for radiological exposure detection. Radiat Prot Dosim. 2012;148(1):20–33. doi:10.1093/rpd/ncq599.
Kaspler P, Chen R, Hyrien O, Jelveh S, Bristow RG, Hill RP. Biodosimetry using radiation-induced micronuclei in skin fibroblasts. Int J Radiat Biol. 2011;87(8):824–38. doi:10.3109/09553002.2011.582927.
Coy SL, Cheema AK, Tyburski JB, Laiakis EC, Collins SP, Fornace A Jr. Radiation metabolomics and its potential in biodosimetry. Int J Radiat Biol. 2011;87(8):802–23. doi:10.3109/09553002.2011.556177.
Sharma M, Halligan BD, Wakim BT, Savin VJ, Cohen EP, Moulder JE. The urine proteome for radiation biodosimetry: effect of total body vs. local kidney irradiation. Health Phys. 2010;98(2):186–95. doi:10.1097/HP.0b013e3181b17cbd.
Paul S, Barker CA, Turner HC, McLane A, Wolden SL, Amundson SA. Prediction of in vivo radiation dose status in radiotherapy patients using ex vivo and in vivo gene expression signatures. Radiat Res. 2011;175(3):257–65.
Paul S, Amundson SA. Gene expression signatures of radiation exposure in peripheral white blood cells of smokers and non-smokers. Int J Radiat Biol. 2011;87(8):791–801.
Filiano AN, Fathallah-Shaykh HM, Fiveash J, Gage J, Cantor A, Kharbanda S, et al. Gene expression analysis in radiotherapy patients and C57BL/6 mice as a measure of exposure to ionizing radiation. Radiat Res. 2011;176(1):49–61.
Pogosova-Agadjanyan EL, Fan W, Georges GE, Schwartz JL, Kepler CM, Lee H, et al. Identification of radiation-induced expression changes in nonimmortalized human T cells. Radiat Res. 2011;175(2):172–84.
Turtoi A, Brown I, Schlager M, Schneeweiss FH. Gene expression profile of human lymphocytes exposed to (211)At alpha particles. Radiat Res. 2010;174(2):125–36. doi:10.1667/RR1659.1.
Brengues M, Paap B, Bittner M, Amundson S, Seligmann B, Korn R, et al. Biodosimetry on small blood volume using gene expression assay. Health Phys. 2010;98(2):179–85. doi:10.1097/01.HP.0000346706.44253.5c.
ten Dijke P, Hill CS. New insights into TGF-beta-Smad signalling. Trends Biochem Sci. 2004;29(5):265–73.
Barcellos-Hoff MH. Integrative radiation carcinogenesis: interactions between cell and tissue responses to DNA damage. Semin Cancer Biol. 2005;15(2):138–48.
Nonaka M, Yoshizaki F. Evolution of the complement system. Mol Immunol. 2004;40(12):897–902.
Godekmerdan A, Ozden M, Ayar A, Gursu MF, Ozan AT, Serhatlioglu S. Diminished cellular and humoral immunity in workers occupationally exposed to low levels of ionizing radiation. Arch Med Res. 2004;35(4):324–8.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Omaruddin, R.A., Roland, T.A., James Wallace III, H. et al. Gene expression as a biomarker for human radiation exposure. Human Cell 26, 2–7 (2013). https://doi.org/10.1007/s13577-013-0059-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13577-013-0059-6