Time-Dependent Induction of the Nucleotide Excision Repair Gene XPA and RAD51 in Homologous Recombination in Human Lymphocytes Exposed to Low Doses of Ionizing Radiation

Document Type : Original Paper


1 Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Radiology Technology, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran


Introduction: The aim of the present study was to understand the effect of low-doses of ionizing radiation (LDIR) on repair genes expression in blood samples that were taken from healthy donors. The next purpose was to examine the time-effect on the modified gene expression caused by low-doses of ionizing radiation.
Material and Methods: The RNA of peripheral blood lymphocytes (PBLs) taken from four healthy donors was isolated at different time points after exposure including 4, 24, 48, 72, and 168 hours and then cDNA was synthesized. Modification of XPA and RAD51 expression levels due to LDIR (2, 5, 10 cGy) were evaluated by relative quantitative reverse transcription-polymerase chain reaction.
Results: Significant up-regulation of both repair genes was observed at the 4 and 168 h following to 10 cGy.  Also, this dose could increase expression levels of RAD51 at 48 and 72 h after radiation. For lower doses at 5 cGy, only XPA levels were significantly up-regulated after 168 h. A significant regression was found between the XPA levels and the dose, at 168 h after irradiation to PBLs that can represent a new potential biomarker for biological dosimetry purposes.
Conclusion: The results of this study could support the hypothetical role of the different DNA repair pathways in response to LDIR. This led us to propose a molecular biodosimetry method for ionizing radiation in the range of LDIR.


Main Subjects

  1. Nakano T, Xu X, Salem AM, Shoulkamy MI, Ide H. Radiation-induced DNA–protein cross-links: mechanisms and biological significance. Free Radical Biology and Medicine. 2017;107:136-45.
  2. Han W, Yu K. Ionizing radiation, DNA double strand break and mutation. Advances in Genetics research. 2010;4:197-210.
  3. Ghosh S, Ghosh A. Activation of DNA damage response signaling in mammalian cells by ionizing radiation. Free Radical Research. 2021:1-35.
  4. Santivasi WL, Xia F. Ionizing radiation-induced DNA damage, response, and repair. Antioxid Redox Signal. 2014;21:251-9.
  5. Alonso‐González C, González A, Martínez‐Campa C, Gómez‐Arozamena J, Cos S. Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double‐strand DNA break repair. J Pineal Res. 2015;58:189-97.
  6. Udayakumar D, Pandita RK, Horikoshi N, Liu Y, Liu Q, Wong K-K, et al. Torin2 suppresses ionizing radiation-induced DNA damage repair. Radiat Res. 2016;185:527-38.
  7. Ma X-J, Shang L, Zhang W-M, Wang M-R, Zhan Q-M. Mitotic regulator Nlp interacts with XPA/ERCC1 complexes and regulates nucleotide excision repair (NER) in response to UV radiation. Cancer Lett. 2016;373:214-21.
  8. Toossi MTB, Azimian H, Soleymanifard S, Vosoughi H, Dolat E, Rezaei AR, et al. Regulation of XPA could play a role in inhibition of radiation-induced bystander effects in QU-DB cells at high doses. Journal of Cancer Research and Therapeutics. 2020;16(8):68.
  9. Bahreyni-Toossi MT, Vosoughi H, Azimian H, Rezaei AR, Momennezhad M. In vivo exposure effects of 99mTc-methoxyisobutylisonitrile on the FDXR and XPA genes expression in human peripheral blood lymphocytes. Asia Oceania Journal of Nuclear Medicine and Biology. 2018;6(1):32.
  10. Toprani SM, Das B. Radio-adaptive response of base excision repair genes and proteins in human peripheral blood mononuclear cells exposed to gamma radiation. Mutagenesis. 2015;30(5):663-76.
  11. Hu L-B, Chen Y, Meng X-D, Yu P, He X, Li J. Nucleotide excision repair factor XPC ameliorates prognosis by increasing the susceptibility of human colorectal cancer to chemotherapy and ionizing radiation. Frontiers in oncology. 2018;8:290.
  12. Ensminger M, Löbrich M. One end to rule them all: non-homologous end-joining and homologous recombination at DNA double-strand breaks. The British journal of radiology. 2020;93(1115):20191054.
  13. Xiang C, Wu X, Zhao Z, Feng X, Bai X, Liu X, et al. Nonhomologous end joining and homologous recombination involved in luteolin-induced DNA damage in DT40 cells. Toxicology in Vitro. 2020;65:104825.
  14. Bahreyni-Toossi M-T, Dolat E, Khanbabaei H, Zafari N, Azimian H. microRNAs: Potential glioblastoma radiosensitizer by targeting radiation-related molecular pathways. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2019;816:111679.
  15. Shen W, Ma Y, Qi H, Wang W, He J, Xiao F, et al. Kinetics model of DNA double-strand break repair in eukaryotes. DNA Repair. 2021:103035.
  16. Jaafar L, Podolsky RH, Dynan WS. Long-term effects of ionizing radiation on gene expression in a zebrafish model. PloS one. 2013;8(7):e69445.
  17. Roy L, Gruel G, Vaurijoux A. Cell response to ionising radiation analysed by gene expression patterns. Annali dell'Istituto superiore di sanita. 2009;45:272-7.
  18. Fält S, Holmberg K, Lambert B, Wennborg A. Long-term global gene expression patterns in irradiated human lymphocytes. Carcinogenesis. 2003;24:1837-45.
  19. Bae S, Kim K, Cha HJ, Choi Y, Shin SH, An I-S, et al. Low-dose γ-irradiation induces dual radio-adaptive responses depending on the post-irradiation time by altering microRNA expression profiles in normal human dermal fibroblasts. International journal of molecular medicine. 2015;35(1):227-37.
  20. Bahreyni Toossi MT, Najafi Amiri M, Sankian M, Azimian H, Abdollahi Dehkordi S, Khademi S. INF/IL-4 increases after the low doses of gamma radiation in BALB/c spleen lymphocytes. Iranian Journal of Medical Physics. 2019;16(4):264-9.
  21. Sabagh M, Chaparian A. Evaluation of Blood Parameters of the Medical Radiation Workers. Iranian Journal of Medical Physics. 2019;16(6):439-43.
  22. Cheng G-H, Ning W, Jiang D-F, Hong-Guang Z, Zhang Q, Jian-Feng W, et al. Increased levels of p53 and PARP-1 in EL-4 cells probably related with the immune adaptive response induced by low dose ionizing radiation in vitro. Biomed Environ Sci. 2010;23:487-95.
  23. Koval L, Proshkina E, Shaposhnikov M, Moskalev A. The role of DNA repair genes in radiation-induced adaptive response in Drosophila melanogaster is differential and conditional. Biogerontology. 2020;21:45-56.
  24. Goldberg Z, Schwietert CW, Lehnert B, Stern R, Nami I. Effects of low-dose ionizing radiation on gene expression in human skin biopsies. Int J Radiat Oncol Biol Phys. 2004;58:567-74.
  25. Grudzenski S, Raths A, Conrad S, Rübe CE, Löbrich M. Inducible response required for repair of low-dose radiation damage in human fibroblasts. Proc Natl Acad Sci 2010;107:14205-10.
  26. Knops K, Boldt S, Wolkenhauer O, Kriehuber R. Gene expression in low-and high-dose-irradiated human peripheral blood lymphocytes: possible applications for biodosimetry. Radiat Res. 2012;178(4):304-12.
  27. Swartz HM, Williams BB, Flood AB. Overview of the principles and practice of biodosimetry. Radiat Environ Biophys. 2014;53:221-32.
  28. Tucker JD, Joiner MC, Thomas RA, Grever WE, Bakhmutsky MV, Chinkhota CN, et al. Accurate gene expression-based biodosimetry using a minimal set of human gene transcripts. Int J Radiat Oncol Biol Phys. 2014;88:933-9.
  29. Paul S, Amundson SA. Development of gene expression signatures for practical radiation biodosimetry. Int J Radiat Oncol Biol Phys. 2008;71:1236-44. e76.
  30. Vosoughi H, Azimian H, Khademi S, Rezaei A-R, Najafi Amiri M, Vaziri-Nezamdoost F, et al. PHA stimulation may be useful for FDXR gene expression-based biodosimetry. Iran J Basic Med Sci. 2020;23:449-53.
  31. Goldberg Z, Schwietert CW, Lehnert B, Stern R, Nami I. Effects of low-dose ionizing radiation on gene expression in human skin biopsies. International Journal of Radiation Oncology* Biology* Physics. 2004;58(2):567-74.
  32. Bladen CL, Navarre S, Dynan WS, Kozlowski DJ. Expression of the Ku70 subunit (XRCC6) and protection from low dose ionizing radiation during zebrafish embryogenesis. Neurosci Lett. 2007;422:97-102.
  33. Tilton SC, Markillie LM, Hays S, Taylor RC, Stenoien DL. Identification of differential gene expression patterns after acute exposure to high and low doses of low-LET ionizing radiation in a reconstituted human skin tissue. Radiat Res. 2016;186:531-8.
  34. Sudprasert W, Navasumrit P, Ruchirawat M. Effects of low-dose gamma radiation on DNA damage, chromosomal aberration and expression of repair genes in human blood cells. Int J Hyg Environ Health. 2006;209:503-11.





Volume 19, Issue 1
January and February 2022
Pages 9-13
  • Receive Date: 21 November 2020
  • Revise Date: 18 February 2021
  • Accept Date: 23 February 2021