Absence of mutations in the human interferon alpha-2b gene in workers chronically exposed to ionising radiation

Open access

Abstract

Individuals chronically exposed to low-level ionising radiation (IR) run the risk of harmful and long-term adverse health effects, including gene mutations and cancer development. The search for reliable biomarkers of IR exposure in human population is still of great interest, as they may have a great implementation potential for the surveillance of occupationally exposed individuals. In this context, and considering previous literature, this study aimed to identify mutations in the human interferon alpha-2b (hIFNα-2b) as a potential biomarker of occupational chronic low-dose IR exposure linking low-IR exposure to the effects on haematopoiesis and reduced immunity. The analysis was performed in the genomic DNA of 51 uranium miners and 38 controls from Kazakhstan, and in 21 medical radiology workers and 21 controls from Italy. hIFNα-2b gene mutations were analysed with the real-time polymerase chain reaction (PCR) or Sanger sequencing. However, none of the investigated workers had the hIFNα-2b mutation. This finding highlights the need for further research to identify biomarkers for early detection of health effects associated with chronic low-dose IR exposure.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Godekmerdan A Ozden M Ayar A Gursu FM Ozan AT Serhatlioglu S. Diminished cellular and humoral immunity in workers occupationally exposed to low levels of ionizing radiation. Arch Med Res 2004;35:324–8. doi: 10.1016/j.arcmed.2004.04.005

  • 2. Oskouii MR Refahi S Pourissa M Tabarraei Y. Assessment of humoral immunity in workers occupationally exposed to low levels of ionizing radiation. Life Sci J 2013;10:58–62.

  • 3. Rödel F Frey B Multhoff G Gaipl U. Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Lett 2015;356:105–13. doi: 10.1016/j.canlet.2013.09.015

  • 4. Voos P Fuck S Weipert F Babel L Tandl D Meckel T Hehlgans S Fournier C Moroni A Rödel F Thiel G. Ionizing radiation induces morphological changes and immunological modulation of Jurkat cells. Front Immunol 2018;9:922. doi: 10.3389/fimmu.2018.00922

  • 5. Shahid S Mahmood N Nawaz Chaundhry M Sheikh S Ahmad N. Mutations of the human interferon alpha-2b (hIFN-α2b) gene in occupationally protracted low dose radiation exposed personnel. Cytokine 2015;73:181–9. doi: 10.1016/j.cyto.2015.02.008

  • 6. Shahid S Mahmood N Nawaz Chaundhry M Ahmad N. Mutations of the human interferon alpha-2b (hIFN-α2b) gene in low-dose natural terrestrial ionizing radiation exposed dwellers. Cytokine 2015;76:294–302. doi: 10.1016/j.cyto.2015.05.011

  • 7. Parmar S Platanis LC. Interferons: mechanisms of action and clinical implications. Curr Opin Oncol 2003;15:431–9. PMID: 14624225

  • 8. Brandacher G Winkler C Schroecksnadel K Margreiter R Fuchs D. Antitumoral activity of interferon-gamma involved in impaired function in cancer patients. Curr Drug Metab 2006;7:599–612. doi: 10.2174/138920006778017768

  • 9. Bose A Baral R. IFNα2b stimulated release of IFNgamma differentially regulates T cell and NK cell mediated tumor cell cytotoxicity. Immunol Lett 2007;108:68–77. doi: 10.1016/j.imlet.2006.10.002

  • 10. Levin D Schneider WM Hoffmann HH Yarden G Busetto AG Manor O Sharma N Rice CM Schreiber G. Multifaceted activities of type I interferon are revealed by a receptor antagonist. Sci Signal 2014;7:ra50. doi: 10.1126/scisignal.2004998

  • 11. Shahid S Nawaz Chaudry M Mahmood N Sheikh S. Mutation of the human interferon alpha-2b gene in brain tumor patients exposed to different environmental conditions. Cancer Gene Ther 2015;22:246–61. doi: 10.1038/cgt.2015.12

  • 12. Shahid S Nawaz Chaundhry M Mahmood N. Mutations of the human interferon alpha-2b (hIFNα-2b) gene in cancer patients receiving radiotherapy. Am J Cancer Res 2015;5:2455–66. PMCID: PMC4568781

  • 13. Kazymbet PK Bakhtin MM Imasheva BS. Population radiation level of the north Kazakhstan by natural sources of ionized radiation. Astana Med J 2006;1:26-8.

  • 14. Maffei F Angelini S Forti GC Lodi V Mattioli S Hrelia P. Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors. Mutagenesis 2002;17:405–9. doi: 10.1093/mutage/17.5.405

  • 15. Trott K Rosemann M. Molecular mechanisms of radiation carcinogenesis and the linear non-threshold dose response model of radiation risk estimation. Radiat Environ Biophys 2000;39:79–87. PMID: 10929376

  • 16. Gadhia P Shah N Nahata S Patel S Patel K Pithawala M Tamakuwala D. Cytogenetic analysis of radiotherapeutic and diagnostic workers occupationally exposed to radiations. Int J Human genet 2004;4:65. doi. 10.1080/09723757.2004.11885872

  • 17. Jin YW Na YJ Lee YJ An S Lee JE Jung M Kim H Nam SY Kim CS Yang KH Kim SU Kim WK Park WY Yoo KY Kim CS Kim JH. Comprehensive analysis of time-and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-doses ionizing radiation. Oncol Rep 2008;19:135–44. doi: 10.3892/or.19.1.135

  • 18. Kazakh Ministry of Justice Centre of Legal Information. О Стратегическом плане Агентства Республики Казахстан по атомной энергии на 2012 – 2016 годы [Strategic Plan of the Atomic Energy Agency of the Republic of Kazakhstan for 2012–2016 in Russian]. [displayed 27 March 2019]. Available at http://www.adilet.zan.kz/rus/docs/P1200001806/links

  • 19. Angelini S Kumar R Carbone F Maffei F Cantelli-Forti G Violante FS Lodi V Curti S Hemmini K Hrelia P. Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphismsin DNA repair genes. Mutat Res 2005;570:105–17. doi: 10.1016/j.mrfmmm.2004.10.007

  • 20. Milić M Rozgaj R Kašuba V Jazbec AM Starčević B Lyzbicki B Ravegnini G Zenesini C Musti M Hrelia P Angelini S. Polymorpisms in DNA repair genes: link with biomarkers of the CBMN cytome assay in hospital workers chronically exposed to low doses of ionising radiation. Arh Hig Rada Toksikol 2015;66:109–20. doi: 10.1515/aiht-2015-66-2655

  • 21. Mumbrekar KD Goutham HV Vadhiraja BM Bola Sadashiva SR. Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals. DNA Repair 2016;40:27–34. doi: 10.1016/j.dnarep.2016.02.006

  • 22. Sinitsky MY Minina VI Asanov MA Yuzhalin AE Ponasenko AV Druzhinin VG. Association of DNA repair gene polymorphisms with genotoxic stress in underground coal miners. Mutagenesis 2017;32:501–9. doi: 10.1093/mutage/gex018

  • 23. Doukali H Ben Salah G Ben Rhouma B Hajjaji M Jaouadi A Belguith-Mahfouth N Masmoudi ML Ammar-Keskes L Kamoun H. Cytogenetic monitoring of hospital staff exposed to ionizing radiation: optimize protocol considering DNA repair genes variability. Int J Radiat Biol 2017;93:1283–8. doi: 10.1080/09553002.2017.1377361

  • 24. Angelini S Kumar R Carbone F Bermejo JL Maffei F Cantelli-Forti G Hemminki K Hrelia P. Inherited susceptibility to bleomycin-induced micronuclei: Correlating polymorphisms in GSTT1 GSTM1 and DNA repair genes with mutagen sensitivity. Mutat Res 2008;638:90–7. doi: 10.1016/j.mrfmmm.2007.09.001

  • 25. Milić M Rozgaj R Kašuba V Jazbec AM Hrelia P Angelini S. The influence of individual genome sensitivity in DNA damage repair assessment in chronic professional exposure to low doses of ionizing radiation. In: Chen CC editor. Selected topics in DNA repair. London: IntechOpen; 2011 [displayed 27 March 2019]. Available at https://www.intechopen.com/books/selected-topics-in-dna-repair/the-influence-of-individual-genome-sensitivity-in-dna-damage-repair-assessment-in-chronic-profession

  • 26. Fenech M Knasmueller S Bolognesi C Bonassi S Holland N Migliore L Palitti F Natarajan AT Kirsch-Volders M. Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans. Mutat Res 2016;770:12–25. doi: 10.1016/j.mrrev.2016.04.008

  • 27. Angelini S Bermejo JL Ravegnini G Sammarini G Hrelia P. Application of the lymphocyte Cytochinesis-Block Micronucleus Assay to population exposed to petroleum and its derivatives: results from a systematic review and meta-analysis. Mutat Res 2016;770:58–72. doi: 10.1016/j.mrrev.2016.03.001

  • 28. Siama Z Zosang-Zuali M Vanlalruati A Jagetia GC Pau KS Kumar NS. Chronic low dose exposure of hospital workers to ionizing radiation leads to incresed micronuclei frequency and reduced antioxidants in their peripheral blood lymphocytes. Int J Radiat Biol 2019. doi: 10.1080/09553002.2019.1571255. [Epub ahead of print]

  • 29. Khisroon M Khan A Naseem M Ali N Khan S Rasheed SB. Evaluation of DNA damage in lymphocytes of radiology personnel by comet assay. J Occup Health 2015;57:268–74. doi: 10.1539/joh.14-0154-OA

  • 30. Korzeneva IB Kostuvk SV Ershova LS Osipov AN Zhuraleva VF Pankratova GV Porokhovnik LN Veiko NN. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation. Mutat Res 2015;779:1–15. doi: 10.1016/j.mrfmmm.2015.05.004

  • 31. Gulati S Yadav A Kumar N Kanupriya Aggarwal NK Kumar R Gupta R. Effect of GSTM1 and GSTT1 polymorphisms on genetic damage in humans population exposed to radiation from mobile towers. Arch Environ Contam Toxicol 2016;70:615–25. doi: 10.1007/s00244-015-0195-y

  • 32. Gaetani S Monaco F Bracci M Ciarapica V Impollonia G Valentino M Tomasetti M Santarelli L Amati M. DNA damage response in workers exposed to low-dose ionising radiation. Occup Environ Med 2018;75:724–9. doi: 10.1136/oemed-2018-105094

  • 33. Maffei F Angelini S Forti GC Violante FS Lodi V Mattioli S Hrelia P. Spectrum of chromosomal aberrations in peripheral lymphocyte of hospital workers occupationally exposed to low doses of ionizing radiation. Mutat Res 2004;547:91–9. doi: 10.1016/j.mrfmmm.2003.12.003

  • 34. Tawn EJ Curwen GB Jonas P Gillies M Hodgson L Cadwell KK. Chromosome aberrations determined by FISH in radiation workers from the Sellafield nuclear facility. Radiat Res 2015;184:296–303. doi: 10.1667/RR14125.1

  • 35. Djokovic-Davidovic J Milovanovic A Milovanovic J Antic V Gajic M. Analysis of chromosomal aberrations frequency haematological parameters and received doses by nuclear medicine professionals. J BUON 2016;21:1307–15. PMID: 27837637

  • 36. Tawn EJ Curwen GB Riddel AE. Chromosome aberrations in workers occupationally exposed to tritium. J Radiol Prot 2018;38:N9–16. doi: 10.1088/1361-6498/aab0d0

  • 37. Shirley B Li Y Knoll JHM Rogan PK. Expedite radiation biodosimetry by automated dicentric chromosome identification (ADCI) and dose estimation. J Vis Exp 2017;127:56245. doi: 10.3791/56245

  • 38. Lenzi M Cocchi V Hrelia P. Flow cytometry vs optical microscopy in the evaluation of the genotoxic potential of xenobiotic compounds. Cytometry B Clin Cytom 2018;94:696–706. doi: 10.1002/cyto.b.21546

Search
Journal information
Impact Factor

IMPACT FACTOR 2018: 1.436
5-year IMPACT FACTOR: 1.606

CiteScore 2018: 1.53

SCImago Journal Rank (SJR) 2018: 0.358
Source Normalized Impact per Paper (SNIP) 2018: 0.608

Metrics
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 229 229 41
PDF Downloads 124 124 13