mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2023.047mes-43Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕORIGINAL RESEARCHЧастота инверсий в хромосомах Т-лимфоцитов у облученных жителей Южного УралаFrequency of inversions in the T-lymphocyte chromosomes of exposed residents of the Southern UralsКривощаповаЯ. В.KrivoshchapovaYa. V.

Челябинск

Chelyabinsk

ВозиловаА. В.VozilovaA. V.

Яна Владимировна Кривощапова

ул. Воровского, д. 68А, г. Челябинск, 454141

Chelyabinsk

Уральский научно-практический центр радиационной медицины Федерального медико-биологического агентстваРоссияUrals Research Center for Radiation Medicine of the Federal Medical Biological AgencyRussian Federation2023221020242547076Copyright © Кривощапова Я.В., Возилова А.В., 20242024Кривощапова Я.В., Возилова А.В.Krivoshchapova Y.V., Vozilova A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/43

Известно, что ионизирующее излучение — это один из факторов, повышающих частоту хромосомных перестроек. Распространенность инверсий была мало изучена из-за сложности их выявления общепринятым методом дифференциальной окраски. Комплексное изучение хроматина, его сложных перестроек стало возможно с применением высокотехнологичного молекулярно-генетического метода — флуоресцентной in situ гибридизации (FISH). Целью исследования было изучить частоту инверсий с вовлечением теломерных участков хромосом у 36 жителей Южного Урала, почти все из которых подверглись сочетанному хроническому облучению. Рассчитанные индивидуализированные суммарные дозы от внешнего и внутреннего облучения — от 0,0001 до 4,7 Гр. Инверсии выявляли методом флуоресцентной окраски теломерного участка хромосом. В результате обнаружили, что распространены преимущественно хроматидные инверсии по сравнению с хромосомными вариантами (9 : 0,3 на 100 клеток (p < 0,001). Не выявлено зависимости исследованных показателей от дозы облучения, пола и возраста на момент обследования.

It is well-known that ionizing radiation is among factors increasing the rate of chromosomal rearrangements. The inversion rate was poorly understood due to difficulty of inversion identification by the conventional differential staining method. A comprehensive study of chromatin and its complex rearrangements has become possible with the use of the high-tech molecular genetic method, fluorescence in situ hybridization (FISH). The study was aimed to assess frequency of inversions involving the chromosome telomeric regions in 36 residents of the South Urals, almost all of them were affected by combined chronic exposure. The calculated individualized cumulative external and internal doses were 0.0001–4.7 Gy. Inversions were identified by fluorescence staining of the chromosome telomeric region. It was found that chromatid inversions were more abundant than chromosomal variants (9 : 0.3 per 100 cells (p < 0.001). No relationship between the studied parameters and the absorbed dose, sex and age at the time of the examination was revealed.

хромосомные аберрацииинверсиителомерные районы хромосомионизирующее излучениеFISHрека Течаchromosomal aberrationsinversionstelomeric regions of chromosomesionizing radiationFISHTecha RiverReferencesАклеев А. В., редактор. Последствия радиоактивного загрязнения реки Теча. Челябинск: Книга, 2016; 400 с.Akleev AV, editor. Consequences of radioactive contamination of the river Techa. Chelyabinsk: The Book, 2016; p. 400. Russian.Venkatesan S, Natarajan AT, Hande MP. Chromosomal instability- mechanisms and consequences. Mutat Res Gen Toxicol Environ Mutagen. 2015; 793: 176–84.Venkatesan S, Natarajan AT, Hande MP. Chromosomal instability- mechanisms and consequences Mutat. Res Gen Toxicol Environ Mutagen. 2015; 793: 176–84.Bailey SM, Bedford JS. Studies on chromosome aberration induction: What can they tell us about DNA repair? DNA repair. 2006; 5: 1171– 81.Bailey SM, Bedford JS. Studies on chromosome aberration induction: What can they tell us about DNA repair? DNA repair. 2006; 5: 1171– 81.Cytogenetic analysis for radiation dose assessment: a manual. International Atomic Energy Agency Technical Reports Series. 2001; 405: 30–45.Cytogenetic analysis for radiation dose assessment: a manual. International Atomic Energy Agency Technical Reports Series. 2001; 405: 30–45.Возилова А. В. Оценка влияния хронического облучения на преждевременное старение Т-лимфоцитов человека на основе нестабильных хромосомных аберраций. Медицина экстремальных ситуаций. 2023; 2 (25): 50–5.Vozilova AV. Assessment of the effect of chronic exposure on premature aging of human T-lymphocytes based on unstable chromosome aberrations. Extreme medicine. 2023; 2 (25): 50–5. Russian.Vozilova AV, Shagina NB, Degteva MO, Akleyev AV. Chronic radioisotope effects on residents of the Techa river (Russia) region: cytogenetic analysis more than 50 years after onset of exposure Mutation Research. 2013; 756 (1–2); 115–8.Vozilova AV, Shagina NB, Degteva MO, Akleyev AV. Chronic radioisotope effects on residents of the Techa river (Russia) region: cytogenetic analysis more than 50 years after onset of exposure Mutation Research. 2013; 756 (1–2); 115–8.Bonassi S, Norppa H, Ceppi M, Strömberg U, Vermeulen R, Znaor A, et al. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries. Carcinogenesis. 2008; 29 (6): 1178–83.Bonassi S, Norppa H, Ceppi M, Strömberg U, Vermeulen R, Znaor A, et al. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries. Carcinogenesis. 2008; 29 (6): 1178–83.Eidelman YA, Salnikov IV, Slanina SV, Andreev SG. Chromosome folding promotes intrachromosomal aberrations under radiation- and nuclease-induced DNA breakage. Int J Mol Sci. 2021; 22 (22): 12186. DOI: 10.3390/ijms222212186.Eidelman YA, Salnikov IV, Slanina SV, Andreev SG. Chromosome folding promotes intrachromosomal aberrations under radiation- and nuclease-induced DNA breakage. Int J Mol Sci. 2021; 22 (22): 12186. DOI: 10.3390/ijms222212186.Bunting SF, Nussenzweig A. End-joining, translocations and cancer. Nat Rev Cancer. 2013; 13 (7): 443–54.Bunting SF, Nussenzweig A. End-joining, translocations and cancer. Nat Rev Cancer. 2013; 13 (7): 443–54.Iourov IY, Vorsanova SG, et al. The Cytogenomic “Theory of Evrything” chromohelikosis may underlie chromosomal instability and mosaicism in disease and aging. Int. J. Sci. 2020; 21: 8328.Iourov IY, Vorsanova SG, et al. The Cytogenomic “Theory of Evrything” chromohelikosis may underlie chromosomal instability and mosaicism in disease and aging. Int. J. Sci. 2020; 21: 8328.Puig M, Casillas S, Villatoro S, et al. Human inversions and their functional consequences. Briefings in Functional Genomics. 2015; 14 (5): 369–79.Puig M, Casillas S, Villatoro S, et al. Human inversions and their functional consequences. Briefings in Functional Genomics. 2015; 14 (5): 369–79.Hoffmann AA, Rieseberg LH. Revisiting the impact of inversions in evolution: from population genetic markers to drivers of adaptive shifts and speciation. Annu Rev Ecol Evol Syst. 2008; 39: 21–42.Hoffmann AA, Rieseberg LH. Revisiting the impact of inversions in evolution: from population genetic markers to drivers of adaptive shifts and speciation. Annu Rev Ecol Evol Syst. 2008; 39: 21–42.Ray FA, Zimmerman E, et al. Directional genomic hybridization for chromosomal inversion discovery and detection. Chromosome Res. 2013; 21: 165–74.Ray FA, Zimmerman E, et al. Directional genomic hybridization for chromosomal inversion discovery and detection. Chromosome Res. 2013; 21: 165–74.Livingston GK, Ryan T, Smith TL, et al. Detection of simple, complex, and clonal chromosome translocations induced by internal radioiodine exposure: a cytogenetic follow-up case study after 25 years. Cytogen Genome Res. 2019; 159: 169–81.Livingston GK, Ryan T, Smith TL, et al. Detection of simple, complex, and clonal chromosome translocations induced by internal radioiodine exposure: a cytogenetic follow-up case study after 25 years. Cytogen Genome Res. 2019; 159: 169–81.Luxton J, McKenna M, Lewis A, et al. Telomere length dynamics and DNA damage responses associated with long-duration spaceflight. Cell Rep. 2020; 33 (10): 108457. DOI: 10.1016/j. celrep.2020.108457.Luxton J, McKenna M, Lewis A, et al. Telomere length dynamics and DNA damage responses associated with long-duration spaceflight. Cell Rep. 2020; 33 (10): 108457. DOI: 10.1016/j.celrep.2020.108457.Возилова А. В., Кривощапова Я. В. Исследование частоты инверсий и комплексных транслокаций в Т-лимфоцитах у облученных жителей Южного Урала. Радиационная биология. Радиоэкология. 2022; 62 (4): 408–15.Vozilova AV, Krivoshchapova YaV. Investigation of the frequency of inversions and complex translocations in T-lymphocytes in irradiated residents of the Southern Urals. Radiation Biology. Radioecology. 2022; 62 (4): 408–15. Russian.Vozilova AV, Shagina NB, Degteva MO, et al. Chronic radioisotope effects on residents of the Techa river (Russia) region: cytogenetic analysis more than 50 years after onset of exposure Mutation Research. 2013; 756 (1–2): 115–8.Vozilova AV, Shagina NB, Degteva MO, et al. Chronic radioisotope effects on residents of the Techa river (Russia) region: cytogenetic analysis more than 50 years after onset of exposure Mutation Research. 2013; 756 (1–2): 115–8.Nielsen PE, Egholm M, Berg RH, Buchardt O. Sequence-selective recognition of DNA by strand displacement with a thymine- substituted polyamide. Sci. 1991; 254 (5037): 1497–500.Nielsen PE, Egholm M, Berg RH, Buchardt O. Sequence-selective recognition of DNA by strand displacement with a thymine- substituted polyamide. Sci. 1991; 254 (5037): 1497–500.Ruiz-Herrera A, Nergadze SG, Santagostino M, Giulotto E. Telomeric repeats far from the ends: Mechanisms of origin and role in evolution. Cytogenetic and Genome Research. 2009; 122 (3–4): 219–28.Ruiz-Herrera A, Nergadze SG, Santagostino M, Giulotto E. Telomeric repeats far from the ends: Mechanisms of origin and role in evolution. Cytogenetic and Genome Research. 2009; 122 (3–4): 219–28.Bolzán AD. Interstitial telomeric sequences in vertebrate chromosomes: Origin, function, instability and evolution. Mutation Research. 2017; 773: 51–65.Bolzán AD. Interstitial telomeric sequences in vertebrate chromosomes: Origin, function, instability and evolution. Mutation Research. 2017; 773: 51–65.Nergadze SG, Santagostino MA, Salzano A, Mondello C, Giulotto E. Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution. Genome Biology. 2007; 8 (12): R260.Nergadze SG, Santagostino MA, Salzano A, Mondello C, Giulotto E. Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution. Genome Biology. 2007; 8 (12): R260.Marzec P, Armenise C, Pérot G, Roumelioti FM, Basyuk E, Gagos S, et al. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers. Cell. 2015; 160 (5): 913–27.Marzec P, Armenise C, Pérot G, Roumelioti FM, Basyuk E, Gagos S, et al. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers. Cell. 2015; 160 (5): 913–27.Muntoni A, Reddel RR. The first molecular details of ALT in human tumor cells. Human Molecular Genetics. 2005; 14 (2): 191–6.Muntoni A, Reddel RR. The first molecular details of ALT in human tumor cells. Human Molecular Genetics. 2005; 14 (2): 191–6.Gonzalez-Suarez I, Gonzalo S, Crosstalk between chromatin structure, nuclear compartmentalization, and telomere biology. Cytogenetic and Genome Research. 2009; 122 (3–4): 202–10.Gonzalez-Suarez I, Gonzalo S, Crosstalk between chromatin structure, nuclear compartmentalization, and telomere biology. Cytogenetic and Genome Research. 2009; 122 (3–4): 202–10.Льюин Б. Гены. М.: БИНОМ. Лаборатория знаний, 2011; 896 с.Lewin B. Genes. M.: BINOM. Laboratoriya znaniy, 2011; 896 с. Russian.

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