The role of radiation induced oxidative stress as a regulator of radio-adaptive responses



Various sources of radiation including radiofrequency, electromagnetic radiation (EMR), low- dose X-radiation, low-level microwave radiation and ionizing radiation (IR) are indispensable parts of modern life. In the current review, we discussed the adaptive responses of biological systems to radiation with a focus on the impacts of radiation-induced oxidative stress (RIOS) and its molecular downstream signaling pathways.

Materials and Methods

A comprehensive search was conducted in Web of Sciences, PubMed, Scopus, Google Scholar, Embase, and Cochrane Library. Keywords included Mesh terms of “radiation”, “electromagnetic radiation”, “adaptive immunity”, “oxidative stress”, and “immune checkpoints”. Manuscript published up until December 2019 were included.


RIOS induces various molecular adaptors connected with adaptive responses in radiation exposed cells. One of these adaptors includes p53 which promotes various cellular signaling pathways. RIOS also activates the intrinsic apoptotic pathway by depolarization of the mitochondrial membrane potential and activating the caspase apoptotic cascade. RIOS is also involved in radiation-induced proliferative responses through interaction with mitogen-activated protein kinases (MAPks) including p38 MAPK, ERK, and c-Jun N-terminal kinase (JNK). Protein kinase B (Akt)/phosphoinositide 3-kinase (PI3K) signaling pathway has also been reported to be involved in RIOS-induced proliferative responses. Furthermore, RIOS promotes genetic instability by introducing DNA structural and epigenetic alterations, as well as attenuating DNA repair mechanisms. Inflammatory transcription factors including macrophage migration inhibitory factor (MIF), nuclear factor κB (NF-κB), and signal transducer and activator of transcription-3 (STAT-3) paly major role in RIOS-induced inflammation.


In conclusion, RIOS considerably contributes to radiation induced adaptive responses. Other possible molecular adaptors modulating RIOS-induced responses are yet to be divulged in future studies.

Figure 1. Major sources of increased cellular oxidative stress following radiation. Either ionizing or non-ionizing radiation can induce ROS and decrease reductive content within cells. This is usually warranted either through disturbing the electron transfer chain within the mitochondrial membrane, or direct dissociation of water molecule into free radicals.

Figure 3. Potential roles of radiation-induced oxidative stress in apoptosis, proliferation, and cell senescence. Increased ROS can promote apoptotic pathways by both induction of p53 signaling and activation of intrinsic caspase-dependent apoptosis. Also, increased ROS content of cells exposed to radiation may promote the proliferative response by p38 MAPK signaling pathway. Moreover, it was suggested that MAPK pathway can lead to cell senescence through induction of p16 downstream pathways.

Figure 4. The potential effects of radiation-induced oxidative stress on DNA biology. ROS produced by radiation may promote direct toxicity toward DNA by introducing structural changes and compromising DNA integrity. This subsequently activates p53 signaling followed by cell cycle arrest and apoptosis. Oxidative stress has been noted to reduce the activity of DNA methyl transferase enzyme and in this manner, may participate in epigenetic regulation of gene expression. On the other hand, ROS can also alter the activity of DNA repair mechanisms such as nucleotide excision-based repair.

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