Background: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency,
it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to
its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues.
Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance
of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs,
increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy.
Discussion: So far, several studies have proposed different targets such as cyclooxygenase-2 (COX-2),
some toll-like receptors (TLRs), mitogen-activated protein kinases (MAPKs) etc., for the amelioration
of radiation toxicity and enhancing tumor response. NADPH oxidase includes five NOX and two dual
oxidases (DUOX1 and DUOX2) subfamilies that through the production of superoxide and hydrogen
peroxide, play key roles in oxidative stress and several signaling pathways involved in early and late
effects of ionizing radiation. Chronic ROS production by NOX enzymes can induce genomic instability,
thereby increasing the risk of carcinogenesis. Also, these enzymes are able to induce cell death, especially
through apoptosis and senescence that may affect tissue function. ROS-derived NADPH oxidase
causes apoptosis in some organs such as intestine and tongue, which mediate inflammation. Furthermore,
continuous ROS production stimulates fibrosis via stimulation of fibroblast differentiation and
collagen deposition. Evidence has shown that in contrast to normal tissues, the NOX system induces
tumor resistance to radiotherapy through some mechanisms such as induction of hypoxia, stimulation of
proliferation, and activation of macrophages. However, there are some contradictory results. Inhibition
of NADPH oxidase in experimental studies has shown promising results for both normal tissue protection
and tumor sensitization to ionizing radiation.
Conclusion: In this article, we aimed to review the role of different subfamilies of NADPH oxidase in
radiation-induced early and late normal tissue toxicities in different organs.