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a wide range of doses, and ability to be performed in various tissues such as lymphocytes, splenocytes, buccal cells, bone marrow cells, skin, and plucked hairs( Raavi et al., 2021).
As a result, gamma-H2AX assay may serve as a sensitive and specific biomarker of ionizing radiation exposure. This approach can identify low levels of radiation exposure that other measuring methods cannot. Furthermore, because gamma-H2AX foci can remain for hours after radiation exposure, this approach can detect radiation exposure even after DNA damage has occurred( Chen et al., 2024; Ferlazzo et al., 2017).
The use of gamma-H2AX as a biomarker of ionizing radiation exposure has been extensively researched, both for medical applications( such as monitoring radiation dose in patients undergoing radiation therapy) and for assessing radiation dose in workers exposed to radiation in their workplace( Djuzenova et al., 2015; Liu et al., 2022; Sgouros et al., 2020). This is a significant example of how DNA damage and cellular response mechanisms have been used in the creation of helpful technologies in health and safety( Khazaei Monfared et al., 2023).
3.3 Gamma-H2AX as an indicator of DNA damage in external radiation therapy
External radiation therapy causes DNA damage in bodily cells, such as blood cells and hematopoietic cells in the bone marrow( Richardson, 2011). The gamma-H2AX biomarker can directly indicate the extent of DNA damage directly related to the patient’ s hematotoxicity. Higher radiation doses will cause more DNA damage and gamma-H2AX foci, increasing the risk of hematotoxicity. This is related to bone marrow damage caused by radiation exposure( Derlin et al., 2021). As a result, it is critical to monitor the hematological status of patients receiving radiation therapy constantly.
A comparison of gamma-H2AX foci levels before and after radiation therapy reveals the quantity of DNA damage and may also indicate the severity of hematotoxicity in patients. The gamma-H2AX assay could be an effective technique for personalizing radiation therapy and identifying patients at high risk of hematotoxicity( Lassmann et al., 2010). Further research relating this biomarker to hematological results could aid in developing safer and more effective therapeutic techniques and lower the risk of radiation-induced side effects.
In nuclear medicine, g-H2AX is used to evaluate DNA damage at the cellular level during external radiation therapy and isotope radiation therapy evaluations. One of its key applications is determining an individual’ s radiation sensitivity. Clinical investigations have indicated that this biomarker can be used to assess DNA damage in radiation therapy patients and help decide the best radiation dose for each individual.
Several clinical trials have investigated using g-H2AX in external beam radiation therapy. Sak et al.( 2007) found an increase in g-H2AX foci in patients’ peripheral blood cells after radiation therapy, with a clear link between the number of foci and radiation dose received. These findings support using g-H2AX as a sensitive, non-invasive indicator of DNA damage that can provide a direct picture of the biological response to radiation therapy. Additionally, g-H2AX can potentially monitor the effectiveness of radiation treatment in nuclear medicine.
In a study of head and neck cancer patients, Li et al.( 2013) found that higher levels of g-H2AX foci before therapy were associated with more DNA damage and better outcomes. g-H2AX can assess patients’ radiation sensitivity, allowing clinicians to regulate dosages more precisely, reduce side effects, and improve therapeutic success. In addition, g-H2AX can be combined with other medicines, such as chemotherapy or radiation therapy and DNA repair inhibitors.
The use of g-H2AX in nuclear medicine has the potential to be a helpful tool in personalizing radiation therapy. This biomarker enables real-time monitoring of DNA damage in patients and more exact therapy adjustments. g-H2AX identifies individuals’ radiation sensitivity, leading to more effective and focused therapy with fewer adverse effects.
3.4 Gamma-H2AX and radiopharmaceutical therapy
Radiopharmaceutical therapy uses beta and alpha particles to eliminate cancer cells while minimizing damage to healthy tissue surrounding the tumor. As the energy passes through the tissues, it accumulates inside the cells, causing DNA SSB and DSBs. To ensure optimal destruction of the targeted cells while minimizing ionization interactions with healthy cells, it is critical to consider multiple factors such as the particle energy, emission range, and linear energy transfer( LET), in addition to the physical or biochemical characteristics( phenotype), dimensions or physical extent( size), and location of the target cells within the tumors( Khazaei Monfared et al., 2023).
Peptide receptor radionucleotide therapy( PRRT) is a generally safe treatment however modest hematologic damage is expected. Continuous PRRT treatment raises the danger of accumulating unrepaired DNA damage in normal tissues, possibly leading to genetic instability and carcinogenesis. Aside from acute myelotoxicity, four out of 504 individuals in one study developed myelodysplastic syndrome( MDS)( Denoyer et al., 2015; Vinnikov and Belyakov, 2022). To reduce the toxicity of PRRT, organ dosimetry using radioisotope biodistribution and kinetics is recommended. Imagebased dosimetry can not accurately predict blood problems in particular people. There is no agreement on the best radiobiologic model for short-range, low-dose-rate radiopeptides. Studying DNA damage at the single-cell level may provide light on PRRT-induced toxicity pathways and aid in predicting the biological effects of radiation dosage in vivo( Denoyer et al., 2015).
Gamma-H2AX has been used as a“ biodosimeter” to assess radiation exposure in peripheral blood lymphocytes( PBLs) after external body irradiation because of its immediate reaction and sensitivity( Raavi et al., 2021; Ramadhani et al., 2020; Vinnikov and Belyakov, 2022). Recent studies suggest that the gamma-H2AX assay may identify radiosensitive patients with early chronic radiation-induced normal-tissue damage and guide individualized treatment( Djuzenova et al., 2013; Lobachevsky et al., 2016).
Radiopharmaceutical-induced DNA damage is more complex than that caused by external ionizing radiation. This is due to the nature of radionuclide emissions, the