Expression of DDB2, XPC, and GADD45 Genes after Whole Body Gamma Irradiation

Document Type : Original Paper

Authors

1 Department of Radiology, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran & Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Radiology, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Radiology, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences

4 Department of Radiology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran & 2Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), Shiraz University of Medical Sciences, Shiraz, Iran

5 Department of Laboratory Medicine, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Introduction: The stimulation of DNA repair mechanisms is an immediate response to radiation-induced damage. Monitoring the expression of DNA-repair-related genes would be a beneficial method to identify bio-dosimeter of radiation exposure, particularly for challenging low-dose radiation. In this study, we aimed to evaluate the effect of different low doses of gamma radiation on the expression of DDB2, XPC, and GADD45A genes involved in DNA-damage repair mechanisms.
Material and Methods: Forty-eight male rats were divided into a control group and five exposure groups. The latter groups exposed to various doses of γ-rays (Co-60) ranged from 20 mGy to 1000 mGy. 24 h after irradiation, isolated lymphocytes from collected blood samples were used for evaluating gene expression levels by real-time quantitative polymerase chain reaction (qRT-PCR). Data were expressed as means ± SD and were statistically evaluated using one‑way ANOVA or Kruskal-Wallis test. P value<0.05 was considered as a significant value.
Results: DDB2, GADD45A, and XPC expression remained unchanged at a dose of 20 mGy, and at doses above 20 mGy, they changed significantly. XPC and GADD45A altered significantly at 50 mGy while DDB2 changed significantly after exposure to 100, 500, and 1000 mGy.
Conclusion: Low doses of gamma radiation (less than 1 Gy) can significantly affect DDB2, XPC, and GADD45A expression, three central genes in the DNA-damage repair process. The extent of the gene expression changes at higher doses of 100, 500, and 1000 mGy seems more severe than that of their lower counterparts (50 mGy).

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References

  1. Håkansson P, Hofer A, Thelander L. Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells. Journal of Biological Chemistry. 2006 Mar 24;281(12):7834-41.
  2. Khanna A. DNA Damage in Cancer Therapeutics: A Boon or a Curse? Targeting DNA Damage in Cancer. Cancer research. 2015 Jun 1;75(11):2133-8.
  3. Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. International journal of radiation biology. 1994 Jan 1;65(1):27-33.
  4. Yamamori T, Yasui H, Yamazumi M, Wada Y, Nakamura Y, Nakamura H, et al. Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint. Free Radical Biology and Medicine. 2012 Jul 15;53(2):260-70.
  5. Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA repair. 2004 Aug 1;3(8-9):889-900.
  6. Valerie K, Yacoub A, Hagan MP, Curiel DT, Fisher PB, Grant S, Dent P. Radiation-induced cell signaling: inside-out and outside-in. Molecular cancer therapeutics. 2007 Mar;6(3):789-801.
  7. Houtgraaf JH, Versmissen J, van der Giessen WJ. A concise review of DNA damage checkpoints and repair in mammalian cells. Cardiovascular Revascularization Medicine. 2006 Jul 1;7(3):165-72.
  8. Torgovnick A, Schumacher B. DNA repair mechanisms in cancer development and therapy. Frontiers in genetics. 2015 Apr 23;6:157.
  9. Bahreyni-Toossi MT, Fardid R, Rezaee A, Sadr-nabavi A, Rafatpanah H, Bolbolian M. Expression of apoptotic genes can distinguish radiation workers from normal population. International Journal of Low Radiation. 2012;8(5-6):388-99.
  10. Hoglund, E. Blomquist, J. Carlsson, B. Stenerlow E. DNA damage induced by radiation of different linear energy transfer: initial fragmentation. International journal of radiation biology. 2000 Jan 1;76(4):539-47.
  11. Penninckx S, Cekanaviciute E, Degorre C, Guiet E, Viger L, Lucas S, et al. Dose, LET and strain dependence of radiation-induced 53BP1 foci in 15 mouse strains ex vivo introducing novel DNA damage metrics. Radiation research. 2019 Jul;192(1):1-2.
  12. Tu W, Dong C, Fu J, Pan Y, Kobayashi A, Furusawa Y, et al. Both irradiated and bystander effects link with DNA repair capacity and the linear energy transfer. Life sciences. 2019 Apr 1;222:228-34.
  13. Rühm W, Azizova T, Bouffler S, Cullings HM, Grosche B, Little MP, et al. Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates. Journal of radiation research. 2018 Apr 1;59(suppl_2):ii1-0.
  14. Desouky O, Ding N, Zhou G. Targeted and non-targeted effects of ionizing radiation. Journal of Radiation Research and Applied Sciences. 2015 Apr 1;8(2):247-54.
  15. Little JB. Genomic instability and bystander effects: a historical perspective. Oncogene. 2003 Oct;22(45):6978-87.
  16. Morgan WF. Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?. Oncogene. 2003 Oct;22(45):7094-9.
  17. Hoeijmakers JH. DNA damage, aging, and cancer. New England Journal of Medicine. 2009 Oct 8;361(15):1475-85.
  18. Hustedt N, Durocher D. The control of DNA repair by the cell cycle. Nature cell biology. 2017 Jan;19(1):1-9.
  19. Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutation Research/Reviews in Mutation Research. 2002 Jun 1;511(2):145-78.
  20. 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.
  21. Criswell T, Leskov K, Miyamoto S, Luo G, Boothman DA. Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene. 2003 Sep;22(37):5813-27.
  22. Fei P, El-Deiry WS. P53 and radiation responses. Oncogene. 2003 Sep;22(37):5774-83.
  23. Gudkov AV, Komarova EA. The role of p53 in determining sensitivity to radiotherapy. Nature Reviews Cancer. 2003 Feb;3(2):117-29.
  24. Puar YR, Shanmugam MK, Fan L, Arfuso F, Sethi G, Tergaonkar V. Evidence for the involvement of the master transcription factor NF-κB in cancer initiation and progression. Biomedicines. 2018 Jul 27;6(3):82.
  25. Rao X, Huang X, Zhou Z, Lin X. An improvement of the 2ˆ (–delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostatistics, bioinformatics and biomathematics. 2013 Aug;3(3):71.
  26. Stoyanova T, Roy N, Kopanja D, Bagchi S, Raychaudhuri P. DDB2 decides cell fate following DNA damage. Proceedings of the National Academy of Sciences. 2009 Jun 30;106(26):10690-5.
  27. Bagchi S, Raychaudhuri P. Damaged-DNA binding protein-2 drives apoptosis following DNA damage. Cell division. 2010 Dec;5(1):1-5.
  28. Visweswaran S, Joseph S, Hegde V, Annalakshmi O, Jose MT, Perumal V. DNA damage and gene expression changes in patients exposed to low-dose X-radiation during neuro-interventional radiology procedures. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2019 Aug 1;844:54-61.
  29. Zhao L, Si CS, Yu Y, Lu JW, Zhuang Y. Depletion of DNA damage binding protein 2 sensitizes triple‐negative breast cancer cells to poly ADP‐ribose polymerase inhibition by destabilizing Rad51. Cancer science. 2019 Nov;110(11):3543-52.
  30. Wang YC, Huang JL, Lee KW, Lu HH, Lin YJ, Chen LF, et al. Downregulation of the DNA repair gene DDB2 by arecoline is through p53’s DNA-binding domain and is correlated with poor outcome of head and neck cancer patients with betel quid consumption. Cancers. 2020 Jul 25;12(8):2053..
  31. Li S, Lu X, Feng JB, Tian M, Wang J, Chen H, et al. Developing gender-specific gene expression biodosimetry using a panel of radiation-responsive genes for determining radiation dose in human peripheral blood. Radiation Research. 2019 Oct;192(4):399-409.
  32. Long XH, Zhao ZQ, He XP, Wang HP, Xu QZ, An J, et al. Dose-dependent expression changes of early response genes to ionizing radiation in human lymphoblastoid cells. International journal of molecular medicine. 2007 Apr 1;19(4):607-15.
  33. Han N, Yuan F, Xian P, Liu N, Liu J, Zhang H, et al. GADD45a mediated cell cycle inhibition is regulated by P53 in bladder cancer. OncoTargets and therapy. 2019;12:7591.
  34. Visweswaran S, Joseph S, Dhanasekaran J, Paneerselvam S, Annalakshmi O, Jose MT, et al. Exposure of patients to low doses of X-radiation during neuro-interventional imaging and procedures: Dose estimation and analysis of γ-H2AX foci and gene expression in blood lymphocytes. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2020 Aug 1;856:503237.
  35. Li D, Dai C, Yang X, Li B, Xiao X, Tang S. GADD45a regulates olaquindox-induced DNA damage and S-phase arrest in human hepatoma G2 cells via JNK/p38 pathways. Molecules. 2017 Jan 13;22(1):124.
  36. Amundson SA, Do KT, Fornace Jr AJ. Induction of stress genes by low doses of gamma rays. Radiation research. 1999 Sep 1;152(3):225-31.
  37. Grace M, McLeland CB, Blakely WF. Real-time quantitative RT-PCR assay of GADD45 gene expression changes as a biomarker for radiation biodosimetry. International Journal of Radiation Biology. 2002 Jan 1;78(11):1011-21.
  38. Wilson KD, Sun N, Huang M, Zhang WY, Lee AS, Li Z, et al. Effects of ionizing radiation on self-renewal and pluripotency of human embryonic stem cells. Cancer research. 2010 Jul 1;70(13):5539-48.
  39. Zhao JZ, Mucaki EJ, Rogan PK. Predicting ionizing radiation exposure using biochemically-inspired genomic machine learning. F1000Research. 2018;7.
Iranian Journal of Medical Physics
Volume 19, Issue 4
July and August 2022
Pages 207-213

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History

  • Receive Date: 18 July 2021
  • Revise Date: 21 September 2021
  • Accept Date: 28 September 2021

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