Open research questions in Effects of Radiation Exposure
33 unresolved questions extracted from the limitations and future-work sections of 345 Effects of Radiation Exposure papers in our library. Each links back to the study that raised it.
What the literature leaves open
We recommend performing further studies to evaluate the long term changes in the salivary glands, associated with exposure to gamma irradiation. Also further studies are required to elicit the role of AgNPs combined with other radioprotective agents in attenuating the radiation-induced alterations. ORCID Asmaa Sayed Shahin: https://orcid.org/0009-0001-9287-6311 Mohamed Emad El-Din Ibrahim: https://orcid.org/0009-0008-0017-0436 Doaa Mahmoud Shuaib: https://orcid.org/0000-0002-6166-5159 Wafaa Mahmoud Abdullah: https://orcid.org/0009-0008-3874-1871 https://doi.org/10.5115/acb.26.073 1. Talapko J, Talapko D, Katalinić D, Kotris I, Erić I, Belić D, Vasilj Mihaljević M, Vasilj A, Erić S, Flam J, Bekić S, Matić S, Škrlec I. Health effects of ionizing radiation on the human body. Medicina (Kaunas) 2024;60:653. 2. Chandra RA, Keane FK, Voncken FEM, Thomas CR Jr. Contemporary radiotherapy: present and future. Lancet 2021;398: 171-84. 3. Wang L, Lynch C, Pitroda SP, Piffkó A, Yang K, Huser AK, Liang HL, Weichselbaum RR. Radiotherapy and immunology. J Exp Med 2024;221:e20232101. 4. Boraks G, Tampelini FS, Pereira KF, Chopard RP. Effect of ionizing radiation on rat parotid gland. Braz Dent J 2008;19:73-6. 5. Wu YH, Yao QT, Liu SH, Song XB, Yakupu AP, Lu LD, Shi L, Xu H. Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats. Eur J Oral Sci 2021;129: e12785. 6. Zhang H, Jacob JA, Jiang Z, Xu S, Sun K, Zhong Z, Varadharaju N, Shanmugam A. Hepatoprotective effect of silver nanoparticles synthesized using aqueous leaf extract of Rhizophora apiculata. Int J Nanomedicine 2019;14:3517-24. 7. Zhao Y, Zhang Y, Huang Y, Fan Y, Zhao L, Gao L, Mo D, Wang X, Wang D. Radioprotective effects and mechanism of Dicliptera chinensis polysaccharide on submandibular gland injury induced by radiation in rats. J Radiat Res Appl Sci 2024;17: 100872. 8. Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr 2019;2019:lgz016. Anat Cell Biol Asmaa Sayed Shahin, et alwww.acbjournal.org 21 9. Barazzuol L, Coppes RP, van Luijk P. Prevention and treatment of radiotherapy‐induced side effects. Mol Oncol 2020;14:1538- 54. 10. Najahi-Missaoui W, Arnold RD, Cummings BS. Safe nanoparticles: are we there yet? Int J Mol Sci 2020;22:385. 11. Arozal W, Monayo ER, Barinda AJ, Perkasa DP, Soetikno V, Nafrialdi N, Louisa M. Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats. Front Med (Lausanne) 2022;9:867497. nanoparticles on the submandibular salivary gland toxicity induced by methotrexate in male rats. Arch Oral Biol 2023;152: 105717. 24. Carvalho-Silva JM, Reis ACD. Anti-inflammatory action of silver nanoparticles in vivo: systematic review and meta-analysis. Heliyon 2024;10:e34564. 25. Wu VWC, Leung KY.
Acute radiation-induced changes in the submandibular salivary gland and possible radioprotective role of silver nanoparticles: a histological, immunohistochemical, and ultrastructural study · 2026 · DOISince the first RC cells were established in 1972, radioresistance research has remained a major obstacle in achieving optimal therapeutic outcomes. Despite decades of research, its multifactorial nature continues to challenge the identification of all the molecular and cellular mechanisms involved. RC radioresistance arises from a complex interplay of processes, including modulation of the TME, through immune cell interactions, fibroblast activation, and hypoxia, that promote survival under therapeutic pressure while enhancing invasive and metastatic potential. It also accounts for intrinsic tumour cell responses, cell cycle arrest, DNA damage repair, and the induction of stemness, as well as patients overall status and tumour characteristics. Moreover, accumulating evidence suggests that metabolic reprogramming enables RC cells to adapt to the oxidative and energetic stress imposed by radiotherapy. Therefore, we propose that this metabolic adaptability, which counteracts ionising radiationinduced cell death, should be recognised as the “seventh R” of radiobiology. Collectively, these dynamic alterations within the tumour ecosystem underscore the complexity of RC radioresistance and highlight interesting candidates for clinical studies. The emergence of 3D culture systems, such as spheroids and PDOs, together with animal models, has revolutionised our ability to study tumour responses under conditions that better mimic in vivo architecture and microenvironmental interactions. These systems have already provided crucial insights into the mechanisms by which RC cells and their surrounding microenvironment resist ionising radiation, not only advancing the discovery of biomarkers for basic research. However, they can serve as pre-clinical companions to validate whether candidate biomarkers truly benefit from radiosensitising agents or immune-targeted combinations, as well as for fractiondose personalisation. Furthermore, how does this influence practice? By positioning the pre-clinical models as the vehicle for implementing biomarker-guided radiotherapy. Some of the reviewed biomarkers, namely PRDM15, XIAP, and survivin, as well as the TME composition, before and after LARC treatment, have already shown prognostic and predictive value. Nevertheless, prospective validation in nCRT/TNT trials would be crucial. Other biomarkers, especially focusing on metabolic alterations in cholesterol and tryptophan metabolism, have already shown, prospectively, a decrease in tumour burden as radiosensitisation agents. Nevertheless, several gaps continue to hinder biomarker research. Most DDR, cell death, TME, and metabolic markers are derived from heterogeneous preclinical systems, including 2D cultures, 3D spheroids, PDOs, and animal models, that differ substantially in culture conditions, ionising radiation schemes, and endpoint readouts.
The combination of thermal ablation and adoptive NK-cell therapy should be further investigated in clinically relevant sub-lethal ablation settings and broader ablation-time combinations to support future clinical studies.
High-intensity thermal stress enhances adoptive NK-cell cytotoxicity in poorly differentiated hepatocellular carcinoma · 2026 · DOIHowever, it remains unclear whether the observed tissue-sparing effects (TSE) result from biological NTE or simply from physical dose-volume characteristics.
Dose-volume histogram analysis of slit-beam irradiation: biological implications in mouse ex vivo testes · 2026 · DOIHIGHLIGHTSO_LIRadiation-related heart disease is an often under-recognized complication of radiation exposure and radiation therapy, which has no FDA-approved biomarkers for assessing risk.
Serum pro-N-cadherin: a biomarker of cardiac fibrosis and diastolic dysfunction in irradiated non-human primates · 2026 · DOIFurther investigation is needed to determine the risk of tumor oc- currence or secondary malignancies in pediatric patients with brain tumor after RT. The NHIRD also does not provide detailed information on possible brain tumor- or RT-related risk factors such as smoking, diet, genetic variants, structural birth de- fects, types of tumors, location of tumors, brain surgery, radiation dose, treatment volume, fraction size, and image guidance, which could be potential confounding factors and these factors could not be evaluated, necessitating prospective multicenter studies to con- firm results of the present study.
Radiation therapy increases long-term gonadotropin deficiency, hypothalamic-pituitary dysfunction, and brainstem necrosis in pediatric patients with brain tumor · 2026 · DOIThere are some limitations in this study. For some rare variants, including BARD1, BRIP1, CHD1, NF1, PALB2, PMS2, RAD51C/D, TP53 and double heterozygote variants, relatively few patients could be analyzed. The results of these subgroups should be considered exploratory rather than definitive and require confirmation or refutation in larger studies. The comparison groups are limited due to the unknown proportion of risk carriers and the absence of confirmed non-carrier status, which results from the historical collection of data for a study with a different focus. Therefore, gene-specific conclusions are limited in this study, as it cannot be excluded that a small proportion of mutation carriers may be present in the comparison group. It would be valuable for future studies to include a control cohort with confirmed non-carrier status to address this limitation. The breast cancer group has many outlying values > 0.1 B/M in background aberrations compared to other groups. This could have been caused by previous cancer treatment. Background levels of heterogeneity may introduce bias through subtraction, which could potentially influence the final radiosensitivity results. Several factors can influence radiosensitivity. In addition to variant status, which affects DNA repair mechanisms, other genetic modifying variables are present. Other factors that influence radiosensitivity should be considered, such as age, which increases slightly with advancing age, and inflammatory diseases, such as rheumatoid arthritis48, vitiligo39 or lupus erythematosus27 and drugs like chloroquine and kinase inhibitors49. However, no gender-related differences were found50. As several variables can influence radiation sensitivity, it would have been preferable to conduct multivariate regression analyses to capture these interactions more comprehensively and arrive at more nuanced conclusions by taking multiple influencing factors into account simultaneously. This should be considered in future studies involving larger subgroups. Additionally, the FiSH radiosensitivity test should be performed prior to radiotherapy, as high background rates can complicate data interpretation51.
However, considering that the information intensity related to the genotoxic effects of PBV in the literature is still insufficient, reports of further studies with different genotoxicity endpoints will be needed to elucidate the exact genotoxic feature.
Investigation of the genotoxic effects of patent blue V (E131) in human peripheral lymphocytes and <i>in silico</i> molecular docking · 2021 · DOIElectromagnetic irradiation with extremely high frequencies (EHF EMI) and low intensity affects living organisms of a different level of organization, but the mechanism(s) of its influence is still not understood well.
Effect of whole body extremely high frequency electromagnetic irradiation exposure on lipid peroxidation in rats · 2017 · DOISuch behavior could be anticipated for a cell which is lacking the repair system that operates in other (normal) cells when they are exposed to ionizing radiations in the G1 phase of the cell cycle.
Bisquerra Alzina, R. (2013). Cuestiones sobre el bienestar. Madrid: Síntesis 184 páginas. ISBN: 978-84-995881-0-0. DL: M-31.498-2013 · 2014 · DOIIn spite of its notorious reputation over at least 90 years, the precise pathogenesis of ORN has not been fully clarified, which has led to obstacles in the management of the disease.
Myofibroblasts and their resistance to apoptosis: a possible mechanism of osteoradionecrosis · 2012 · DOIThe primary limitation of this study, however, is the timing of CAP intervention, which was initiated at the peak of dermatitis severity.
Assessment of cold atmospheric pressure plasma therapy initiated at peak severity in a mouse model of radiation dermatitis · 2026 · DOIJ expression increases in renal tubular epithelial cells (TECs) following ionizing radiation (IR), its functional role remains poorly understood.
Histone Variant H2A.J Links Epigenetic Reprogramming to Mitochondrial-dependent Kidney Regeneration under Radiation Stress · 2026 · DOIC_LIO_LIThis study lays the foundation for further research into the development of serum pro-N-cadherin as a biomarker for assessing the risk of radiation-related heart disease in humans.
Serum pro-N-cadherin: a biomarker of cardiac fibrosis and diastolic dysfunction in irradiated non-human primates · 2026 · DOIAlthough low-dose colchicine reduces ischemic cardiovascular events in coronary artery disease, the precise molecular mechanisms underlying its vasculoprotective effects remain incompletely defined, and whether it mitigates radiation-associated vascular injury is unknown.
Colchicine Directly Targets Aldehyde Dehydrogenase 2 (ALDH2) to Suppress Radiation-Induced Senescence and Atherosclerosis · 2026 · DOIIn search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored.
Most-cited papers in Effects of Radiation Exposure
- Health Effects of Ionizing Radiation on the Human Body · Medicina · 2024 · 94 citations
- Microbiota-derived I3A protects the intestine against radiation injury by activating AhR/IL-10/Wnt signaling and enhancing the abundance of probiotics · Gut Microbes · 2024 · 85 citations
- S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells suppress ferroptosis and alleviate radiation-induced lung injury and long-term pulmonary fibrosis · Journal of Nanobiotechnology · 2024 · 64 citations
- Co-Assembled Binary Polyphenol Natural Products for the Prevention and Treatment of Radiation-Induced Skin Injury · ACS Nano · 2024 · 63 citations
- Bisquerra Alzina, R. (2013). Cuestiones sobre el bienestar. Madrid: Síntesis 184 páginas. ISBN: 978-84-995881-0-0. DL: M-31.498-2013 · REOP - Revista Española de Orientación y Psicopedagogía · 2014 · 31 citations
- The irradiated human mandible: A quantitative study on bone vascularity · Oral Oncology · 2018 · 30 citations
- Let‐7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin‐8 · Journal of Oral Pathology and Medicine · 2018 · 27 citations
- Investigation of the genotoxic effects of patent blue V (E131) in human peripheral lymphocytes and <i>in silico</i> molecular docking · Drug and Chemical Toxicology · 2021 · 26 citations
- Radiation-induced skin injury in the head and neck region: pathogenesis, clinics, prevention, treatment considerations and proposal for management algorithm · Reports of Practical Oncology & Radiotherapy · 2024 · 23 citations
- Everything you wanted to know about space radiation but were afraid to ask · Journal of Environmental Science and Health Part C · 2021 · 21 citations
Most recent work
- A quantitative proteomics dataset for assessment and prediction of low dose X-ray radiation exposure in mice. · bioRxiv · 2026
- Integrative Therapies for Radiation-Related Toxicities in Hematological Malignancies · Seminars in Radiation Oncology · 2026
- Functional-based multi-omics early prediction of radiation pneumonitis in NSCLC using AI-generated perfusion and ventilation from planning CT · Physics in Medicine & Biology · 2026
- Central and peripheral analgesia in irradiated rats: reserpine-induced pain model · Scientific Reports · 2026
- Restorative effect of Rehmanniae radix praeparata on T-cell and NK-cell-mediated immune reconstitution in mice following radiation-induced injury · Journal of Radiation Research · 2026
- BMSCs alleviate inflammation and inhibit apoptosis in radiation pneumonitis treatment by modulating the NF-κB/NLRP3 signaling pathway · Journal of Radiation Research · 2026
- Contribution of immune cells and cytokines to radiation-induced injury: the key roles and potential targets · Frontiers in Immunology · 2026
- An Ingestion-based Chronic Internal Radiation Model in Caenorhabditis elegans Using Americium Trichloride Reveals Tissue-specific Oxidative Stress and Reproductive Toxicity · Annual Research & Review in Biology · 2026
- The radical-mediated linear-exponential (RMLE) model: integrating radical recombination and oxygen depletion for FLASH radiotherapy · Physics in Medicine & Biology · 2026
- PIKfyve Deficiency Exacerbates Radiation-Induced Intestinal Toxicity · Toxics · 2026
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