首页 » 文章 » 文章详细信息
Dose-Response Volume 18 ,Issue 1 ,2020-03-23
Serum Proteins as New Biomarkers for Whole-Body Exposure to High- and Low-LET Ionizing Radiation
Original Article
Wenjun Wei 1 Hao Bai 1 , 2 Xiu Feng 1 , 2 Junrui Hua 1 Kaiqin Long 1 Jinpeng He 1 Yanan Zhang 1 Nan Ding 1 Jufang Wang 1 , 2 Heng Zhou 1
Show affiliations
Received 2019-11-27, accepted for publication 2020-2-18, Published 2020-03-23

Exposure to ionizing radiation is a major threat to human health and public security. Since the inherent limitations of current methods for indicating radiation exposure, new minimally invasive biomarkers that can be easily and quickly detected at an early stage are needed for optimal medical treatment. Serum proteins are attractive biomarkers and some radiosensitive proteins have been found, but the proteins in response to low-dose and high-linear energy transfer (LET) radiation have not been reported. In this study, mice were whole body exposed to a variety doses of carbon ions and X-rays. We performed Mouse Antibody Array to detect serum proteins expression profiles at 24 hours postirradiation. After conditional screening, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 were further validated using enzyme-linked immunosorbent assay. After exposure to 0.05 to 1 Gy of carbon ions and 0.5 to 4 Gy of X-rays, only IGFBP-3 showed obvious increase with increased doses, both carbon ions and X-rays. Further, IGFBP-3 was detected for observation of its time-dependent changes. The results showed the expression difference of IGFBP-3 presented from 6 to 24 hours post-irradiation by carbon ions and X-rays. Moreover, the receiver–operating characteristic analysis showed that serum IGFBP-3 is efficient to triage exposed individuals with high sensitivity and specificity. These results suggest that serum IGFBP-3 is extremely sensitive to high- and low-LET ionizing radiation and is able to respond at an early stage, which could serve as a novel minimally invasive indicator for radiation exposure.


IGFBP-3;X-rays;carbon ions;biomarkers;serum proteins


© The Author(s) 2020
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).


1. Jufang Wang.Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China; University of Chinese Academy of Sciences, Beijing, China.jufangwang@impcas.ac.cn
2. Heng Zhou.Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.jufangwang@impcas.ac.cn


Wenjun Wei,Hao Bai,Xiu Feng,Junrui Hua,Kaiqin Long,Jinpeng He,Yanan Zhang,Nan Ding,Jufang Wang,Heng Zhou. Serum Proteins as New Biomarkers for Whole-Body Exposure to High- and Low-LET Ionizing Radiation. Dose-Response ,Vol.18, Issue 1(2020)



[1] HY Li, YX He, CX Di, JW Yan et al.. Comparative analysis of the serum proteome for biomarker discovery to reveal hepatotoxicity induced by iron ion radiation in mice. Life Sci. 2016;167:57–66.
[2] L Narici, M Casolino, L Di Fino, M Larosa et al.. Radiation survey in the International Space Station. J Space Weather Spac. 2015;5(37):2–14.
[3] A Andrievski, RC Wilkins. The response of-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures. Int J Radiat Biol. 2009;85(4):369–376.
[4] EH Donnelly, JB Nemhauser, JM Smith, et al. Acute radiation syndrome: assessment and management. South Med J. 2010;103(6):541–546.
[5] L Buckbinder, R Talbott, S Velasco-Miguel, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature.1995;377(6550):646–649.
[6] MMPD Pinto, NFG Santos, A Amaral. Current status of biodosimetry based on standard cytogenetic methods. Radiat Environ Bioph. 2010;49(4):567–581.
[7] W Wei, J He, J Wang, et al. Serum microRNAs as early indicators for estimation of exposure degree in response to ionizing irradiation. Radiat Res. 2017;188(3):342–354.
[8] H Ding, T Wu. Insulin-like growth factor binding proteins in autoimmune diseases. Front Endocrinol. 2018;9:499.
[9] S Bjornsdottir, M Oksnes, M Isaksson, et al. Circadian hormone profiles and insulin sensitivity in patients with Addison’s disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy. Clin Endocrinol. 2015;83(1):28–35.
[10] R Monzavi, P Cohen. IGFs and IGFBPs: role in health and disease. Best Pract Res Clin Endocrinol Metab. 2002;16(3):433–447.
[11] R Renner. Redrawing the dose-response curve. Environ Sci Technol. 2004;38(5):90a–95a.
[12] GR Moshtaghi-Kashanian, F Mirzaee, SH Khalilzadeh. Circadian rhythm of acylated ghrelin, leptin, growth hormone, IGF-1, IGFBP-1 and IGFBP-3. Internat J Endocrinol Metab. 2011;9(4):352–359.
[13] K George, M Durante, H Wu, V Willingham et al.. Chromosome aberrations in the blood lymphocytes of astronauts after space flight. Radiat Res. 2001;156(6):731–738.
[14] NG Burnet, R Wurm, JR Yarnold, JH Peacock et al.. Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity. Lancet. 1992;339(8809):1570–1571.
[15] N Hamada, T Imaoka, S Masunaga, et al. Recent advances in the biology of heavy-ion cancer therapy. J Radiat Res. 2010;51(4):365–383.
[16] O Guipaud. Serum and plasma proteomics and its possible use as detector and predictor of radiation diseases. Adv Exp Med Biol. 2013;990:61–86.
[17] JA Caffrey, DM Hamby. A review of instruments and methods for dosimetry in space. Adv Space Res. 2011;47(4):563–574.
[18] PM Glazer, SP Peretz, R Jensen, S Gibson et al.. ATM-dependent expression of the IGF-I receptor in a pathway regulating radiation response. Int J Radiat Oncol Biol Phys. 2001;51(3):55–55.
[19] G Obe, I Johannes, C Johannes, K Hallman et al.. Chromosomal aberrations in blood lymphocytes of astronauts after long-term space flights. Int J Radiat Biol. 1997;72(6):727–734.
[20] M Bianchi, NO Bianchi, JG Brewen, et al. Evaluation of radiation-induced chromosomal aberrations in human peripheral blood lymphocytes in vitro results of an IAEA-coordinated programme. Mutat Res. 1982;96(2-3):233–242.
[21] MWY Chua, MZ Lin, JL Martin, RC Baxter et al.. Involvement of the insulin-like growth factor binding proteins in the cancer cell response to DNA damage. J Cell Commun Signal. 2015;9(2):167–176.
[22] JA Janssen, RP Stolk, HAP Pols, DE Grobbee et al.. Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels. Clin Endocrinol. 1998;48(4):471–478.
[23] HJ Evans, KE Buckton, GE Hamilton, A Carothers et al.. Radiation-induced chromosome-aberrations in nuclear-dockyard workers. Nature. 1979;277(5697):531–534.
[24] W Schimmerling, FA Cucinotta. Dose and dose rate effectiveness of space radiation. Radiat Prot Dosim. 2006;122(1-4):349–353.
[25] A Ali, R Hashim, FA Khan, et al. Evaluation of insulin-like growth factor-1 and insulinlike growth factor binding protein-3 in diagnosis of growth hormone deficiency in short-stature children. J Ayub Med Coll Abbottabad. 2009;21(3):40–45.
[26] RC. BaxterInsulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions. J Cell Commun Signal. 2013;7(3):179–189.
[27] N Kinoshita, K Sueki, K Sasa, et al. Assessment of individual radionuclide distributions from the Fukushima nuclear accident covering central-east Japan. P Natl Acad Sci USA. 2011;108(49):19526–19529.
[28] M Durante, FA Cucinotta. Heavy ion carcinogenesis and human space exploration. Nat Rev Cancer. 2008;8(6):465–472.
[29] X Zhang, C Ye, F Sun, W Wei et al.. Both complexity and location of DNA damage contribute to cellular senescence induced by ionizing radiation. PLoS One. 2016;11(5):e0155725.
[30] KJ Ho, KA Jenrow, SL Brown. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat Oncol J. 2014,32(3):103–115.
[31] C Menard, D Johann, M Lowenthal, et al. Discovering clinical biomarkers of ionizing radiation exposure with serum proteomic analysis. Cancer Res. 2006;66(3):1844–1850.
[32] K Rothkamm, S Barnard, EA Ainsbury, et al. Manual versus automated gamma-H2AX foci analysis across five European laboratories: can this assay be used for rapid biodosimetry in a large scale radiation accident? Mutat Res-Gen Tox En. 2013;756(1-2):170–173.
[33] M Sproull, T Kramp, A Tandle, U Shankavaram et al.. Serum amyloid a as a biomarker for radiation exposure. Radiat Res. 2015;184(1):14–23.
[34] NL Anderson, NG Anderson. The human plasma proteome—history, character, and diagnostic prospects. Mol Cell Proteomics. 2002;1(11):845–867.
[35] W Wenjun, W Jufang, H Jinpeng, X Xiaodong et al.. Serum microRNA as noninvasive indicator for space radiation. Acta Astronaut. 2018;152:101–104.
[36] L Xu, XL Qi, SL Duan, et al. MicroRNAs: potential biomarkers for disease diagnosis. Bio-Med Mater Eng. 2014;24(6):3917–3925.
浏览 180次
下载全文 11次
评分次数 0次
用户评分 0.0分
分享 0次