Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Mar;13(1):3-16.
doi: 10.1007/s12079-018-0473-3. Epub 2018 Jun 17.

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

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
Affiliations
Review

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

Bagher Farhood et al. J Cell Commun Signal. 2019 Mar.

Abstract

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.

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

PubMed Disclaimer

Conflict of interest statement

No

Figures

Fig. 1
Fig. 1
Mechanisms of radiation toxicity via activation of redox system by intra and intercellular mediators. a; a single irradiated cell induces ROS production which amplify radiation toxicity, leading to more production of ROS. Necrosis and apoptosis cause stimulation macrophages and lymphocytes T to produce several inflammatory or anti-inflammatory cytokines. This is associated with increased redox activity in irradiated cells, as well as in other adjacent non-irradiated cells.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ameziane-El-Hassani R, Talbot M, de Souza Dos Santos MC, Al Ghuzlan A, Hartl D, Bidart J-M, De Deken X, Miot F, Diallo I, De Vathaire F, Schlumberger M, Dupuy C. NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an exposure to irradiation. Proc Natl Acad Sci U S A. 2015;112:5051–5056. - PMC - PubMed
    1. Anscher MS. Targeting the TGF-β1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy. The Oncologist. 2010;15:350–359. - PMC - PubMed
    1. Anscher MS, Thrasher B, Rabbani Z, Teicher B, Vujaskovic Z. Antitransforming growth factor-beta antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation. Int J Radiat Oncol Biol Phys. 2006;65:876–881. - PubMed
    1. Archambeau JO, Tovmasyan A, Pearlstein RD, Crapo JD, Batinic-Haberle I. Superoxide dismutase mimic, MnTE-2-PyP(5+) ameliorates acute and chronic proctitis following focal proton irradiation of the rat rectum. Redox Biol. 2013;1:599–607. - PMC - PubMed
    1. Autsavapromporn N, de Toledo SM, Little JB, Jay-Gerin JP, Harris AL, Azzam EI. The role of gap junction communication and oxidative stress in the propagation of toxic effects among high-dose alpha-particle-irradiated human cells. Radiat Res. 2011;175:347–357. - PMC - PubMed

LinkOut - more resources