Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation

  • Bagher Farhood
  • Nasser Hashemi Goradel
  • Keywan Mortezaee
  • Neda Khanlarkhani
  • Ensieh Salehi
  • Maryam Shabani Nashtaei
  • Dheyauldeen Shabeeb
  • Ahmed Eleojo Musa
  • Hengameh Fallah
  • Masoud NajafiEmail author


Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1β, TNF-α, TGF-β, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators.


Radiation Cohort effect Bystander effect Non-targeted effect Radiation toxicity Radiation disaster Radiotherapy Intracellular communication Cytokines Redox system Mitigation Carcinogenesis 


Compliance with ethical standards

Conflict of interest



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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  • Bagher Farhood
    • 1
  • Nasser Hashemi Goradel
    • 2
  • Keywan Mortezaee
    • 3
  • Neda Khanlarkhani
    • 4
  • Ensieh Salehi
    • 4
  • Maryam Shabani Nashtaei
    • 4
    • 5
  • Dheyauldeen Shabeeb
    • 6
    • 7
  • Ahmed Eleojo Musa
    • 6
    • 8
  • Hengameh Fallah
    • 9
  • Masoud Najafi
    • 10
    Email author
  1. 1.Department of Medical Physics and Radiology, Faculty of Paramedical SciencesKashan University of Medical SciencesKashanIran
  2. 2.Department of Medical Biotechnology, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  3. 3.Department of Anatomy, School of MedicineKurdistan University of Medical SciencesSanandajIran
  4. 4.Department of Anatomy, School of MedicineTehran University of Medical SciencesTehranIran
  5. 5.Infertility Department, Shariati HospitalTehran University of Medical SciencesTehranIran
  6. 6.Department of Medical Physics & Biomedical Engineering, School of MedicineTehran University of Medical SciencesTehranIran
  7. 7.Department of Physiology, College of MedicineUniversity of MisanMisanIraq
  8. 8.Research Center for Molecular and Cellular ImagingTehran University of Medical SciencesTehranIran
  9. 9.Department of Chemistry, Faculty of ScienceIslamic Azad UniversityArakIran
  10. 10.Radiology and Nuclear Medicine Department, School of Paramedical SciencesKermanshah University of Medical SciencesKermanshahIran

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