Medical Radiology and radiation safety Medical Radiology and radiation safety Медицинская радиология и радиационная безопасность 1024-6177 2618-9615 46725 10.12737/1024-6177-2021-66-5-5-10 Радиационная биология Radiation biology Радиационная биология Influence of Powerful Non-Ionizing Terahertz Radiation on Healthy and Tumor Human Cells of Neural Origin ВЛИЯНИЕ МОЩНОГО НЕИОНИЗИРУЮЩЕГО ТЕРАГЕРЦОВОГО ИЗЛУЧЕНИЯ НА ЗДОРОВЫЕ И ОПУХОЛЕВЫЕ КЛЕТКИ ЧЕЛОВЕКА НЕЙРАЛЬНОГО ПРОИСХОЖДЕНИЯ Шаталова Р. О. Shatalova R. O. Гурова C. А. Gurova S. A. Ревкова В. А. Revkova V. A. Ильина И. В. Ilina I. V. Ситников Д. С. Sitnikov D. S. Обнинский институт атомной энергетики – Национальный исследовательский ядерный университет «МИФИ» (Московский инженерно-физический институт), Обнинск Россия National Research Nuclear University, MEPhi Obninsk Institute for Nuclear Power Engineering, Obninsk, Russia Russian Federation Обнинский институт атомной энергетики – Национальный исследовательский ядерный университет «МИФИ» (Московский инженерно-физический институт), Обнинск. Россия National Research Nuclear University, MEPhi Obninsk Institute for Nuclear Power Engineering, Obninsk, Russia Russian Federation Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий ФМБА России, Москва. Россия Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, Moscow, Russia Russian Federation Объединенный институт высоких температур РАН, Москва Россия Joint Institute for High Temperatures, Moscow, Russia Russian Federation Объединенный институт высоких температур РАН, Москва Россия Joint Institute for High Temperatures, Moscow, Russia Russian Federation 66 5 5 10 01 11 2021 https://zh-szf.ru/en/nauka/article/46725/view

Цель: Изучение влияния мощного импульсного когерентного неионизирующего терагерцового (ТГц) излучения на формирование фокусов двунитевых разрывов ДНК и пролиферативную активность нейрональных клеток человека. Материал и методы: Облучаемые клеточные культуры – нейральные прогениторные клетки, полученные методом прямого репрограммирования (drNPCs), клетки нейробластомы (SK-N-BE). Облучение клеток осуществляется последовательностью импульсов ТГц-излучения с пиковой удельной мощностью ~20 ГВт/см2 и напряженностью электрического поля 2,8 МВ/см. Результаты: Показано, что непродолжительное воздействие (30 мин) не оказывает влияние на пролиферативную активность как нейральных прогениторных клеток, так и клеток нейробластомы. ТГц-излучение не вызывает значимого увеличения фокусов γН2АХ ни в одной из исследуемых линий клеток.

Purpose: Study of the influence of high-power pulses of coherent non-ionizing terahertz (THz) radiation on the formation of foci of double-strand DNA breaks and the proliferative activity of human neuronal cells. Material and methods: Irradiated cell cultures are direct reprogramming neural progenitor cells (drNPCs), neuroblastoma cells (SK-N-BE). Cells are irradiated with a sequence of THz radiation pulses with a peak intensity of ~ 20 GW/cm2 and electric field strength of 2.8 MV/cm. Irradiation lasts 30 mins. Results: There is no statistically significant difference in the number of γH2AX histone foci between experimental and control cell groups. Conclusion: It was shown that a short exposure (30 min) of cells to THz radiation with intensity of 20 GW/cm2 does not affect the proliferative activity of both neural progenitor cells and neuroblastoma cells and does not cause a significant increase in γH2AX foci in any of the studied cell lines.

 неионизирующее излучение терагерцовое излучение гистон Н2АХ пролиферативная активность нейральные стволовые клетки нейробластома SK-N-BE non-ionizing radiation terahertz radiation H2AX histone foci proliferative activity neural stem cells SK-N-BE neuroblastoma

Fröhlich H. Long-range coherence and energy storage in biological systems. Int J Quantum Chem. 1968;2(5):641-9. DOI: 10.1002/qua.560020505. Fröhlich H. Long-range coherence and energy storage in biological systems. Int J Quantum Chem. 1968;2(5):641-9. DOI: 10.1002/qua.560020505. Alexandrov BS, Gelev V, Bishop AR, Usheva A, Rasmussen KØ. DNA breathing dynamics in the presence of a terahertz field. Phys Lett A. 2010;374(10):1214-7. DOI: 10.1016/j.physleta.2009.12.077. Alexandrov BS, Gelev V, Bishop AR, Usheva A, Rasmussen KØ. DNA breathing dynamics in the presence of a terahertz field. Phys Lett A. 2010;374(10):1214-7. DOI: 10.1016/j.physleta.2009.12.077. Titova LV, Ayesheshim AK, Golubov A, Rodriguez-Juarez R, Woycicki R, Hegmann FA, et al. Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue? Sci Rep. 2013;3(1):2363. DOI: 10.1038/srep02363. Titova LV, Ayesheshim AK, Golubov A, Rodriguez-Juarez R, Woycicki R, Hegmann FA, et al. Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue? Sci Rep. 2013;3(1):2363. DOI: 10.1038/srep02363. Ольшевская ЮС, Козлов АС, Петров АК, Запара ТА, Ратушняк АС. Влияние на нейроны in vitro терагерцового (субмиллиметрового) лазерного излучения. Журнал высшей нервной деятельности им. И.П. Павлова. 2009;59(3):353-9.[Olshevskaya YUS, Kozlov AS, Petrov AK, Zapara TA, Ratushnyak AS. Effect of Terahertz (Submillimeter) Laser Radiation on Neurons in Vitro. Journal of Higher Nervous Activity. I.P. Pavlova. 2009; 59 (3): 353-9.] Ol'shevskaya YuS, Kozlov AS, Petrov AK, Zapara TA, Ratushnyak AS. Vliyanie na neyrony in vitro teragercovogo (submillimetrovogo) lazernogo izlucheniya. Zhurnal vysshey nervnoy deyatel'nosti im. I.P. Pavlova. 2009;59(3):353-9.[Olshevskaya YUS, Kozlov AS, Petrov AK, Zapara TA, Ratushnyak AS. Effect of Terahertz (Submillimeter) Laser Radiation on Neurons in Vitro. Journal of Higher Nervous Activity. I.P. Pavlova. 2009; 59 (3): 353-9.] Zapara TA, Treskova SP, Ratushniak AS. Effect of antioxidants on the interaction of terahertz (submillimeter) laser radiation and neuronal membrane. J Surf Investig. 2015;9(5):869-71. Zapara TA, Treskova SP, Ratushniak AS. Effect of antioxidants on the interaction of terahertz (submillimeter) laser radiation and neuronal membrane. J Surf Investig. 2015;9(5):869-71. Cheon H, Paik JH, Choi M, Yang HJ, Son JH. Detection and manipulation of methylation in blood cancer DNA using terahertz radiation. Sci Rep. 2019;9(1):1-10. DOI: 10.1038/s41598-019-42855-x. Cheon H, Paik JH, Choi M, Yang HJ, Son JH. Detection and manipulation of methylation in blood cancer DNA using terahertz radiation. Sci Rep. 2019;9(1):1-10. DOI: 10.1038/s41598-019-42855-x. Tan SZ, Tan PC, Luo LQ, Chi YL, Yang ZL, Zhao XL, et al. Exposure Effects of Terahertz Waves on Primary Neurons and Neuron-like Cells Under Nonthermal Conditions. Biomed Environ Sci. 2019;32(10):739-54. DOI: 10.3967/bes2019.094. Tan SZ, Tan PC, Luo LQ, Chi YL, Yang ZL, Zhao XL, et al. Exposure Effects of Terahertz Waves on Primary Neurons and Neuron-like Cells Under Nonthermal Conditions. Biomed Environ Sci. 2019;32(10):739-54. DOI: 10.3967/bes2019.094. Perera PGT, Appadoo DRT, Cheeseman S, Wandiyanto J V, Linklater D, Dekiwadia C, et al. PC 12 pheochromocytoma cell response to super high frequency terahertz radiation from synchrotron source. Cancers (Basel). 2019;11(2):1-17. DOI: 10.3390/cancers11020162. Perera PGT, Appadoo DRT, Cheeseman S, Wandiyanto J V, Linklater D, Dekiwadia C, et al. PC 12 pheochromocytoma cell response to super high frequency terahertz radiation from synchrotron source. Cancers (Basel). 2019;11(2):1-17. DOI: 10.3390/cancers11020162. Maskey D, Pradhan J, Aryal B, Lee C-M, Choi I-Y, Park K-S, et al. Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity. Brain Res. 2010;1346(Maskey2010):237-46. DOI: 10.1016/j.brainres.2010.05.045. Maskey D, Pradhan J, Aryal B, Lee C-M, Choi I-Y, Park K-S, et al. Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity. Brain Res. 2010;1346(Maskey2010):237-46. DOI: 10.1016/j.brainres.2010.05.045. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo. J Cell Biol. 1999;146(5):905-16. DOI: 10.1083/jcb.146.5.905. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo. J Cell Biol. 1999;146(5):905-16. DOI: 10.1083/jcb.146.5.905. Barnes JL, Zubair M, John K, Poirier MC, Martin FL. Carcinogens and DNA damage. Biochem Soc Trans. 2018 Oct 19;46(5):1213-24. DOI: 10.1042/BST20180519. Barnes JL, Zubair M, John K, Poirier MC, Martin FL. Carcinogens and DNA damage. Biochem Soc Trans. 2018 Oct 19;46(5):1213-24. DOI: 10.1042/BST20180519. Sitnikov DS, Ilina I V, Pronkin AA. Experimental system for studying bioeffects of intense terahertz pulses with electric field strength up to 3.5 MV/cm. Opt Eng. 2020;59(06):061613. DOI: 10.1117/1.OE.59.6.061613.full Sitnikov DS, Ilina I V, Pronkin AA. Experimental system for studying bioeffects of intense terahertz pulses with electric field strength up to 3.5 MV/cm. Opt Eng. 2020;59(06):061613. DOI: 10.1117/1.OE.59.6.061613.full Овчинников АВ, Чефонов ОВ, Ситников ДС, Ильина ИВ, Ашитков СИ, Агранат МБ, Источник терагерцевого излучения с напряженностью электрического поля свыше 1 МВ/см на основе фемтосекундного хром-форстеритового лазера с частотой следования импульсов 100 Гц. Квантовая электроника. 2018;48(6):554-8. [Ovchinnikov AV, Chefonov OV, Sitnikov DS, Il’ina I V, Ashitkov SI, Agranat MB. A source of THz radiation with electric field strength of more than 1 MV cm-1 on the basis of 100-Hz femtosecond Cr : forsterite laser system. Quantum Electron. 2018;48(6):554-8. (In Russian) DOI: 10.1070/ qel16681]. Ovchinnikov AV, Chefonov OV, Sitnikov DS, Il'ina IV, Ashitkov SI, Agranat MB, Istochnik teragercevogo izlucheniya s napryazhennost'yu elektricheskogo polya svyshe 1 MV/sm na osnove femtosekundnogo hrom-forsteritovogo lazera s chastotoy sledovaniya impul'sov 100 Gc. Kvantovaya elektronika. 2018;48(6):554-8. [Ovchinnikov AV, Chefonov OV, Sitnikov DS, Il’ina I V, Ashitkov SI, Agranat MB. A source of THz radiation with electric field strength of more than 1 MV cm-1 on the basis of 100-Hz femtosecond Cr : forsterite laser system. Quantum Electron. 2018;48(6):554-8. (In Russian) DOI: 10.1070/ qel16681]. Sitnikov DS, Romashevskiy SA, Ovchinnikov A V, Chefonov O V, Savel’ev AB, Agranat MB. Estimation of THz field strength by an electro-optic sampling technique using arbitrary long gating pulses. Laser Phys Lett. 2019;16(11):115302. DOI: 10.1088/1612-202X/ab4d56. Sitnikov DS, Romashevskiy SA, Ovchinnikov A V, Chefonov O V, Savel’ev AB, Agranat MB. Estimation of THz field strength by an electro-optic sampling technique using arbitrary long gating pulses. Laser Phys Lett. 2019;16(11):115302. DOI: 10.1088/1612-202X/ab4d56. Ситников ДС, Ильина ИВ, Гурова СА, Шаталова РО, Ревкова ВА. Исследование индукции двунитевых разрывов в фибробластах кожи человека терагерцевым излучением высокой интенсивности. Известия Российской Академии Наук Серия Физическая. 2020;84:1605-16. DOI: 10.31857/s0367676520110277. [Sitnikov DS, Ilina I V, Gurova SA, Shatalova RO, Revkova VA. Studying the Induction of Double-Strand Breaks in Human Fibroblasts by High-Intensity Terahertz Radiation. Bull Russ Acad Sci Phys. 2020;84(11):1370-4. (In Russian) DOI: 10.3103/S1062873820 110-246]. Sitnikov DS, Il'ina IV, Gurova SA, Shatalova RO, Revkova VA. Issledovanie indukcii dvunitevyh razryvov v fibroblastah kozhi cheloveka teragercevym izlucheniem vysokoy intensivnosti. Izvestiya Rossiyskoy Akademii Nauk Seriya Fizicheskaya. 2020;84:1605-16. DOI: 10.31857/s0367676520110277. [Sitnikov DS, Ilina I V, Gurova SA, Shatalova RO, Revkova VA. Studying the Induction of Double-Strand Breaks in Human Fibroblasts by High-Intensity Terahertz Radiation. Bull Russ Acad Sci Phys. 2020;84(11):1370-4. (In Russian) DOI: 10.3103/S1062873820 110-246]. Dhuppar S, Roy S, Mazumder A. γH2AX in the S Phase after UV Irradiation Corresponds to DNA Replication and Does Not Report on the Extent of DNA Damage. Mol Cell Biol. 2020;40(20). DOI: 10.1128/MCB.00328-20. Dhuppar S, Roy S, Mazumder A. γH2AX in the S Phase after UV Irradiation Corresponds to DNA Replication and Does Not Report on the Extent of DNA Damage. Mol Cell Biol. 2020;40(20). DOI: 10.1128/MCB.00328-20. Bourge M, Fort C, Soler M, Satiat-Jeunemaître B, Brown SC. A pulse-chase strategy combining click-EdU and photoconvertible fluorescent reporter: tracking Golgi protein dynamics during the cell cycle. New Phytol. 2015;205(2):938-50. DOI: 10.1111/nph.13069. Bourge M, Fort C, Soler M, Satiat-Jeunemaître B, Brown SC. A pulse-chase strategy combining click-EdU and photoconvertible fluorescent reporter: tracking Golgi protein dynamics during the cell cycle. New Phytol. 2015;205(2):938-50. DOI: 10.1111/nph.13069. Yu T, MacPhail SH, Banáth JP, Klokov D, Olive PL. Endogenous expression of phosphorylated histone H2AX in tumors in relation to DNA double-strand breaks and genomic instability. DNA Repair (Amst). 2006;5(8):935-46. DOI: 10.1016/j.dnarep.2006.05.040. Yu T, MacPhail SH, Banáth JP, Klokov D, Olive PL. Endogenous expression of phosphorylated histone H2AX in tumors in relation to DNA double-strand breaks and genomic instability. DNA Repair (Amst). 2006;5(8):935-46. DOI: 10.1016/j.dnarep.2006.05.040. Sitnikov DS, Ilina I V., Revkova VA, Konoplyannikov MA, Kalsin VA, Baklaushev VP. Effect of high-power pulses of terahertz radiation on cell viability. In: 2020 International Conference Laser Optics (ICLO). IEEE; 2020. p. 1. DOI: 10.1109/ICLO48556.2020.9285431. Sitnikov DS, Ilina I V., Revkova VA, Konoplyannikov MA, Kalsin VA, Baklaushev VP. Effect of high-power pulses of terahertz radiation on cell viability. In: 2020 International Conference Laser Optics (ICLO). IEEE; 2020. p. 1. DOI: 10.1109/ICLO48556.2020.9285431. Nagelkerke A, Span PN. Staining Against Phospho-H2AX (γ-H2AX) as a Marker for DNA Damage and Genomic Instability in Cancer Tissues and Cells. In: Koumenis C, Coussens LM, Giaccia A, Hammond E, editors. Tumor Microenvironment. Springer International Publishing; 2016. p. 1-10. PMID: 27325258 DOI: 10.1007/978-3-319-26666-4_1 Nagelkerke A, Span PN. Staining Against Phospho-H2AX (γ-H2AX) as a Marker for DNA Damage and Genomic Instability in Cancer Tissues and Cells. In: Koumenis C, Coussens LM, Giaccia A, Hammond E, editors. Tumor Microenvironment. Springer International Publishing; 2016. p. 1-10. PMID: 27325258 DOI: 10.1007/978-3-319-26666-4_1