mchsrosМедико-биологические и социально-психологические проблемы безопасности в чрезвычайных ситуацияхMedicо-Biological and Socio-Psychological Problems of Safety in Emergency Situations1995-44412541-7487«The Nikiforov Russian Center of Emergency and Radiation Medicine»10.25016/2541-7487-2026-0-1-52-64mchsros-1218Research ArticleБиологические проблемыBiological IssuesВлияние рассеянного ионизирующего излучения на соседние нормальные клетки: исследование in vitro с использованием модели фибробластовImpact of scattered ionizing radiation on adjacent normal cells: an in-vitro study using a fibroblast modelhttps://orcid.org/0000-0002-6613-0268СихБ. Т.SihB. T.

Baydaa T. Sih – PhD in Physics, Assistant Professor in Nuclear and Environmental Physics. Faculty member.

Al-Jadriya, Baghdad

baydaa.sih@sc.uobaghdad.edu.iqDepartment of Physics, College of Science, University of BaghdadIraq202629032026015264Copyright © Сих Б.Т., 20262026Сих Б.Т.Sih B.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mchsros.elpub.ru/jour/article/view/1218

Актуальность. Рассеянное ионизирующее излучение, возникающее от терапевтических пучков во время лучевой терапии, является недооцененным фактором, способствующим сопутствующему повреждению соседних здоровых тканей, что ухудшает результаты лечения и качество жизни пациентов.Цель. In vitro систематически оценивались биологические эффекты рассеянного гамма-излучения на фибробласты кожи человека, расположенные вблизи облученных клеток рака молочной железы (MCF-7).Методология. Фибробласты подвергали косвенному облучению рассеянными дозами 2,5 Гр и 5 Гр от источника 137Cs с предварительной обработкой антиоксидантом восстановленным глутатионом (GSH) или без нее. Клеточные реакции оценивали в 5 временных точках (1, 24, 48 ч, 5 дней и 10 дней), измеряли жизнеспособность, окислительный стресс (малоновый диальдегид, МДА), повреждение ДНК (кометный анализ), апоптоз (каспаза-3), некроз (ФНО-a) и целостность митохондриальной мембраны (с помощью 3D-проточной цитометрии).Результаты и анализ. Результаты показали, что рассеянное излучение вызывает значительные повреждения фибробластов, зависящие от времени и дозы, характеризующиеся повышенным окислительным стрессом, фрагментацией ДНК, апоптозом, некрозом и митохондриальной дисфункцией, несмотря на отсутствие прямого облучения. Примечательно, что предварительная обработка GSH обеспечила существенную защиту, смягчая эти вредные эффекты, особенно при умеренных дозах.Заключение. Эти результаты подчеркивают критическую необходимость учета рассеянного излучения при планировании лечения и указывают на потенциал антиоксидантных стратегий для защиты окружающих нормальных тканей во время лучевой терапии.

Relevance. Scattered ionizing radiation arising from therapeutic beams during radiotherapy is an underestimated contributor to collateral damage in adjacent healthy tissues, compromising treatment outcomes and patient quality of life.Objective. This in vitro study systematically evaluated the biological effects of scattered gamma radiation on human dermal fibroblasts positioned near irradiated breast cancer (MCF-7) cells.Methodology. Fibroblasts were indirectly exposed to scattered doses of 2.5 Gy and 5 Gy from a 137Cs source, with or without pretreatment using the antioxidant reduced glutathione (GSH). Cellular responses were assessed at five time points (1h, 24h, 48h, 5d, and 10d), measuring viability, oxidative stress (malondialdehyde, MDA), DNA damage (Comet assay), apoptosis (Caspase-3), necrosis (TNF-a), and mitochondrial membrane integrity (via 3D flow cytometry).Results and analysis. The results demonstrated that scattered radiation induces significant timeand dosedependent damage in fibroblasts, characterized by increased oxidative stress, DNA fragmentation, apoptosis, necrosis, and mitochondrial dysfunction, despite the absence of direct irradiation. Notably, GSH pretreatment provided substantial protection by mitigating these deleterious effects, particularly at moderate doses.Conclusion. These findings underscore the critical need to account for scattered radiation during treatment planning and highlight the potential of antioxidant-based strategies to protect surrounding normal tissues during radiotherapy.

Scattered radiationfibroblastoxidative stressDNA damageapoptosisnecrosisradiotherapy side effects.ReferencesAzzam E.I., Jay-Gerin J.P., Pain D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Letters. 2012; 327(1–2):48–60. DOI: 10.1016/j.canlet.2011.12.012.Azzam E.I., Jay-Gerin J.P., Pain D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Letters. 2012; 327(1–2):48–60. DOI: 10.1016/j.canlet.2011.12.012.Barjaktarovic Z., Schmaltz D., Shyla A. [et al.]. Radiation-induced alterations of mitochondria in murine heart at early times after exposure to doses relevant for radiotherapy. International Journal of Radiation Oncology, Biology, Physics. 2011; 80(5):1541–1550. DOI: 10.1016/j.ijrobp.2011.01.040.Barjaktarovic Z., Schmaltz D., Shyla A. [et al.]. Radiation-induced alterations of mitochondria in murine heart at early times after exposure to doses relevant for radiotherapy. International Journal of Radiation Oncology, Biology, Physics. 2011; 80(5):1541–1550. DOI: 10.1016/j.ijrobp.2011.01.040.Bentzen S.M. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nature Reviews Cancer. 2006; 6(9):702–713. DOI: 10.1038/nrc1950.Bentzen S.M. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nature Reviews Cancer. 2006; 6(9):702–713. DOI: 10.1038/nrc1950.Dröge W. Free radicals in the physiological control of cell function. Physiological Reviews. 2002; 82(1):47–95. DOI: 10.1152/physrev.00018.2001.Dröge W. Free radicals in the physiological control of cell function. Physiological Reviews. 2002; 82(1):47–95. DOI: 10.1152/physrev.00018.2001.Forman H.J., Zhang H., Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009; 30(1–2):1–12. DOI: 10.1016/j.mam.2008.08.006.Forman H.J., Zhang H., Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009; 30(1–2):1–12. DOI: 10.1016/j.mam.2008.08.006.Gutteridge J.M.C., Halliwell B. Free radicals and antioxidants in the year 2000: A historical look to the future. Annals of the New York Academy of Sciences. 2000; 899(1):136–147. DOI: 10.1111/j.1749-6632.2000.tb06182.x.Gutteridge J.M.C., Halliwell B. Free radicals and antioxidants in the year 2000: A historical look to the future. Annals of the New York Academy of Sciences. 2000; 899(1):136–147. DOI: 10.1111/j.1749-6632.2000.tb06182.x.Hall E.J., Giaccia A.J. Radiobiology for the Radiologist (8th ed.). Wolters Kluwer. 2018.Hall E.J., Giaccia A.J. Radiobiology for the Radiologist (8th ed.). Wolters Kluwer. 2018.Huang Q., Wu Y., Zhong Z. [et al.]. Protective effects of glutathione on ionizing radiation-induced oxidative stress in human endothelial cells. Journal of Radiation Research. 2011; 52(1):45–51. DOI: 10.1269/jrr.10098.Huang Q., Wu Y., Zhong Z. [et al.]. Protective effects of glutathione on ionizing radiation-induced oxidative stress in human endothelial cells. Journal of Radiation Research. 2011; 52(1):45–51. DOI: 10.1269/jrr.10098.Hussein A.A., Haji S.M. Oxidative stress biomarkers in radiology staff exposed to scattered radiation. Journal of Radiation Research and Applied Sciences. 2023; 16(1):120–128. DOI: 10.1016/j.jrras.2023.01.010.Hussein A.A., Haji S.M. Oxidative stress biomarkers in radiology staff exposed to scattered radiation. Journal of Radiation Research and Applied Sciences. 2023; 16(1):120–128. DOI: 10.1016/j.jrras.2023.01.010.Khalaf H.M., Al-Khazraji A.M., Jasim A.H. Effects of indirect gamma radiation on tissue regeneration in experimental animals. Radiation Physics and Chemistry. 2025; 213:111018. DOI: 10.1016/j.radphyschem.2023.111018.Khalaf H.M., Al-Khazraji A.M., Jasim A.H. Effects of indirect gamma radiation on tissue regeneration in experimental animals. Radiation Physics and Chemistry. 2025; 213:111018. DOI: 10.1016/j.radphyschem.2023.111018.Kim J.H., Brown S.L., Kolozsvary A. [et al.]. Glutathione as a radioprotective agent in ionizing radiationinduced tissue injury. Toxicology Letters. 2009; 190(2):153–159. DOI: 10.1016/j.toxlet.2009.07.019.Kim J.H., Brown S.L., Kolozsvary A. [et al.]. Glutathione as a radioprotective agent in ionizing radiationinduced tissue injury. Toxicology Letters. 2009; 190(2):153–159. DOI: 10.1016/j.toxlet.2009.07.019.Li L., Zhou Z., Parris A.B. [et al.]. Radiation-induced mitochondrial ROS promote mitochondrial dysfunction and cell apoptosis. Cell Death & Disease. 2014; 5(9):e1323. DOI: 10.1038/cddis.2014.295.Li L., Zhou Z., Parris A.B. [et al.]. Radiation-induced mitochondrial ROS promote mitochondrial dysfunction and cell apoptosis. Cell Death & Disease. 2014; 5(9):e1323. DOI: 10.1038/cddis.2014.295.Li X., Fang P., Mai J. [et al.]. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. Journal of Hematology & Oncology. 2014; 7(1):1–19. DOI: 10.1186/1756-87227-19.Li X., Fang P., Mai J. [et al.]. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. Journal of Hematology & Oncology. 2014; 7(1):1–19. DOI: 10.1186/1756-87227-19.Mahdi A.H., Al-Sammarraie H.H., Al-Shammari A.M. Oxidative imbalance in cancer patients undergoing radiation therapy. Reports of Practical Oncology and Radiotherapy. 2024; 29(2):99–107. DOI: 10.5603/RPOR.a2024.0010.Mahdi A.H., Al-Sammarraie H.H., Al-Shammari A.M. Oxidative imbalance in cancer patients undergoing radiation therapy. Reports of Practical Oncology and Radiotherapy. 2024; 29(2):99–107. DOI: 10.5603/RPOR.a2024.0010.Riley P.A. Free radicals in biology: oxidative stress and the effects of ionizing radiation. International Journal of Radiation Biology. 1994; 65(1):27–33. DOI: 10.1080/09553009414550041.Riley P.A. Free radicals in biology: oxidative stress and the effects of ionizing radiation. International Journal of Radiation Biology. 1994; 65(1):27–33. DOI: 10.1080/09553009414550041.Sih B.T., Alqasim A. Selective T-cell depletion in stored whole blood using green-synthesised γ-Fe2O3 nanoparticles with gamma or laser irradiation: A comparative in-vitro study. Radiation Physics and Chemistry. 2026; In Press. DOI: 10.1016/j.radphyschem.2025.113537.Sih B.T., Alqasim A. Selective T-cell depletion in stored whole blood using green-synthesised γ-Fe2O3 nanoparticles with gamma or laser irradiation: A comparative in-vitro study. Radiation Physics and Chemistry. 2026; In Press. DOI: 10.1016/j.radphyschem.2025.113537.Spitz D.R., Azzam E.I., Li J.J., Gius D. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: A unifying concept in stress response biology. Cancer and Metastasis Reviews. 2004; 23(3– 4):311–322. DOI: 10.1023/B:CANC.0000031769.14728.bc.Spitz D.R., Azzam E.I., Li J.J., Gius D. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: A unifying concept in stress response biology. Cancer and Metastasis Reviews. 2004; 23(3– 4):311–322. DOI: 10.1023/B:CANC.0000031769.14728.bc.Srinivasan M., Devipriya N., Kalpana K.B. Glutathione protects against gamma radiation-induced oxidative damage in rats. Free Radical Biology and Medicine. 2002; 33(3):317–325. DOI: 10.1016/S08915849(02)00891-2.Srinivasan M., Devipriya N., Kalpana K.B. Glutathione protects against gamma radiation-induced oxidative damage in rats. Free Radical Biology and Medicine. 2002; 33(3):317–325. DOI: 10.1016/S08915849(02)00891-2.Tofilon P.J., Fike J.R. The radioresponse of the central nervous system: a dynamic process. Radiation Research. 2000; 153(4):357–370. DOI: 10.1667/0033-7587(2000)153[0357:TROTCO]2.0.CO;2.Tofilon P.J., Fike J.R. The radioresponse of the central nervous system: a dynamic process. Radiation Research. 2000; 153(4):357–370. DOI: 10.1667/0033-7587(2000)153[0357:TROTCO]2.0.CO;2.Toulany M., Rodemann H.P. Fibroblasts and their roles in radiation oncology. Radiotherapy and Oncology. 2015; 116(3):277–282. DOI: 10.1016/j.radonc.2015.09.020.Toulany M., Rodemann H.P. Fibroblasts and their roles in radiation oncology. Radiotherapy and Oncology. 2015; 116(3):277–282. DOI: 10.1016/j.radonc.2015.09.020.Wang Y., Schulte B.A., LaRue A.C. Radiation-induced lung injury: cytokine mechanisms and therapeutic targets. Current Drug Targets. 2010; 11(10):1386–1394. DOI: 10.2174/1389450111009011386.Wang Y., Schulte B.A., LaRue A.C. Radiation-induced lung injury: cytokine mechanisms and therapeutic targets. Current Drug Targets. 2010; 11(10):1386–1394. DOI: 10.2174/1389450111009011386.Wu G., Fang Y.Z., Yang S. [et al.]. Glutathione metabolism and its implications for health. Journal of Nutrition. 2004; 134(3):489–492. DOI: 10.1093/jn/134.3.489.Wu G., Fang Y.Z., Yang S. [et al.]. Glutathione metabolism and its implications for health. Journal of Nutrition. 2004; 134(3):489–492. DOI: 10.1093/jn/134.3.489.Yousef M.I. [et al.]. Protective role of antioxidants against gamma radiation-induced oxidative stress in rat tissues. Environmental Toxicology and Pharmacology. 2009; 28(2):219–228. DOI: 10.1016/j.etap.2009.05.002.Yousef M.I. [et al.]. Protective role of antioxidants against gamma radiation-induced oxidative stress in rat tissues. Environmental Toxicology and Pharmacology. 2009; 28(2):219–228. DOI: 10.1016/j.etap.2009.05.002.Zhou H., Ivanov V.N., Hei T.K. Prolonged caspase-3 activation in irradiated and bystander cells: a key factor in the bystander effect. Cancer Letters. 2013; 335(1):133–139. DOI: 10.1016/j.canlet.2013.02.004.Zhou H., Ivanov V.N., Hei T.K. Prolonged caspase-3 activation in irradiated and bystander cells: a key factor in the bystander effect. Cancer Letters. 2013; 335(1):133–139. DOI: 10.1016/j.canlet.2013.02.004.

The authors declare that there are no conflicts of interest present.