Cytogenetic effects of excessive radon exposure depending on the individual dosage of active ribosomal genes

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Abstract

Background. Maintaining radon safety is one of the most critical challenges in modern ecology and genetic toxicology. Radon (222Rn) and its decay daughter products (218Po, 214Po, 214Pb and 214Bi) can interact with biological tissues and induce DNA damage. Because transcribed copies rDNA are necessary for DNA damage repair, we examined whether genomic dosages of active ribosomal genes modulate the genotoxic effects of exposure to high doses of radon.

Materials and methods. Chromosome aberration assay in peripheral blood lymphocytes was performed in pupils of the boarding school of Tashtagol (Kemerovo region, Russia) with long-term resident exposure to radon (n = 345) and in childrenof the Kemerovo Region living in radiation-safe conditions (n = 233). The dose of active (transcription-capable) ribosomal gene (AcRG) in the studied groups has been analyzed using Ag-NORS staining regions of chromosomes and cytogenetic semi-quantitative evaluation method.

Results. A statistically significant increase in the level of chromosome aberrations in exposure group has been revealed compared with the children of the Kemerovo Region living in radiation-safe conditions (p = 0.00001). It was found that the level of chromosomal abnormalities in Tashtagol’s children was higher in medium-dose carriers of AcRG compared to owners of a low dose (4.27 ± 0.22% vs. 3.24 ± 0.29%, p = 0.003). Perhaps the low level of chromosomal aberrations in children with low-dose AcRG is associated with an increase in cell death from damaged DNA under genotoxic exposure to radon.

Conclusion. The obtained results testify to the significant contribution of the individual characteristics of ribosomal genes in the formation of genotoxic effects of exposure to high doses of radon.

About the authors

Anna A. Timofeeva

Federal Research Center of Coal and Coal Chemistry of Siberian Branch of RAS

Author for correspondence.
Email: annateam86@gmail.com
ORCID iD: 0000-0002-9063-0158
SPIN-code: 1542-8153

engineer-technologist of the cytogenetics laboratory

Russian Federation, 18, Sovetsky pr., Kemerovo, 650000

Varvara I. Minina

Federal Research Center of Coal and Coal Chemistry of Siberian Branch of RAS; Kemerovo State University

Email: vminina@mail.ru
ORCID iD: 0000-0003-3485-9123
SPIN-code: 5153-8594

PhD, Associate Professor, Department of genetics

Russian Federation, 18, Sovetsky pr., Kemerovo, 650000; 6, Krasnay street, Kemerovo, 650000

Vladimir G. Druzhinin

Federal Research Center of Coal and Coal Chemistry of Siberian Branch of RAS; Kemerovo State University

Email: druzhinin_vladim@mail.ru
ORCID iD: 0000-0002-5534-2062
SPIN-code: 6277-4704

Doctor of biological Sciences, Professor, head, Department of genetics

Russian Federation, 18, Sovetsky pr., Kemerovo, 650000; 6, Krasnay street, Kemerovo, 650000

Tatyana A. Golovina

Kemerovo State University

Email: goltat86@gmail.com
ORCID iD: 0000-0002-2805-0822

engineer of the Department of Genetics

Russian Federation, 6, Krasnay street, Kemerovo, 650000

Tatyana A. Tolochko

Kemerovo State University

Email: totat@list.ru
ORCID iD: 0000-0003-4645-7009
SPIN-code: 2926-6542

senior teacher of the Department of Genetics

Russian Federation, 6, Krasnay street, Kemerovo, 650000

Alexey V. Larionov

Kemerovo State University

Email: alekseylarionov09@gmail.com
ORCID iD: 0000-0002-7974-6483
SPIN-code: 5360-4410

PhD, senior teacher of the Department of Genetics

6, Krasnay street, Kemerovo, 650000

References

  1. Онищенко Г.Г. О состоянии контроля за радиационной безопасностью населения от природных источников ионизирующего излучения // Здоровье населения и среда обитания. – 2008. – №4. – С.9 – 11. [Onishchenko G.G. O sostoyanii kontrolya za radiatsionnoi bezopasnost'yu naseleniya ot prirodnykh istochnikov ioniziruyushchego izlucheniya. Zdorov'e naseleniya i sreda obitaniya. 2008; (4):9-11. (In Russ.)]
  2. Gawełek E, Drozdzowska B, Fuchs A. Radon as a risk factor of lung cancer. Przegl Epidemiol. 2017. 71(1):90-98.
  3. Minina V., Sinitsky M., Druzhinin V. et al. Chromosome aberrations in peripheral blood lymphocytes of lung cancer patients exposed to radon and air pollution. Eur. J. Cancer Prev. 2016; (1). doi: 10.1097/CEJ.0000000000000270.
  4. Meenakshi C, Sivasubramanian K, Venkatraman B. Nucleoplasmic bridges as a biomarker of DNA damage exposed to radon. Mutat Res. 2017. 814:22-28. doi: 10.1016/j.mrgentox.2016.12.004.
  5. Смыслов А.А., Максимовский В.А., Харламов М.Г. Радон в земной коре и риск радоноопасности // Разведка и охрана недр. – 1995.- № 5. - С.45–53. [Smyslov A.A., Maksimovskii V.A., Kharlamov M.G. Radon v zemnoi kore i risk radonoopasnosti. Razvedka i okhrana nedr. 1995; (5):45-53. (In Russ.)]
  6. Вейко Н.Н., Еголина Н.А., Радзивил Г.Г. и др. Количественные определения повторяющихся последовательностей геномной ДНК человека // Молекулярная биология. – 2003. – Т. 30, №5. – С. 1076-1085. [Veiko N.N., Egolina N.A., Radzivil G.G. i dr. Quantitation of Repetitive Sequences in Human Genomic DNA. Molecular Biology. 2003; 30 (5):1076-1085. (In Russ.)]
  7. Taylor E. F., Martin-Deleon P.A. Familial silver staining patterns of human nucleolus organizer regions (NORs). Amer. J. Human Genet. 1981; (33):67 – 76.
  8. Ляпунова Н. А., Пороховник Л. Н., Косякова Н. В., Мандрон И. А., Цветкова Т. Г. Жизнеспособность носителей хромосомных аномалий зависит от геномной дозы активных рибосомных генов (генов рРНК) // Генетика. – 2017. – Т.53, №6. – С.722 – 731. doi: 10.7868/S0016675817060091. [Lyapunova N.A., Porokhovnik L.N., Kosyakova N.V., Mandron I.A., Tsvetkova T.G. Viability of Carriers of Chromosomal Abnormalities Depends on Genomic Dosage of Active Ribosomal Genes (rRNA Genes). Russian Journal of Genetics. 2017; 53 (6):722-731. (In Russ.)]
  9. Valdez BC, Henning D, So RB. et al. The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with up-stream binding factor. Proc Natl Acad Sci. 2004. 101: 10709–10714.
  10. Grob A, Roussel P, Wright JE, et al. Involvement of SIRT7 in resumption of rDNA transcription at the exit frommitosis. J Cell Sci. 2009. 122:489–498.
  11. McStay B. Nucleolar organizer regions: genomic 'dark matter' requiring illumination. Genes Dev. 2016. 30(14):1598-610. doi: 10.1101/gad.283838.116.
  12. Ляпунова Н. А., Еголина Н. А. Межхромосомный и межиндивидуальный полиморфизм системы рибосомных генов в геноме человека // I Всес. конф. «Геном человека». – 1990 . – С. 170 – 171. [Lyapunova N. A., Egolina N. A. Mezhkhromosomnyi i mezhindividual'nyi polimorfizm sistemy ribosomnykh genov v genome cheloveka. I Vses. konf. «Genom cheloveka». 1990. P. 170 – 171. (In Russ.)]
  13. Барановская Л.И., Цветкова Т. Г., Кравец И. А., Ляпунова Н. А. Выявление активных и репрессированных копий рибосомного гена в индивидуальных ядрышкообразующих районах хромосом // II Всес. конф. «Геном человека». – 1991. – С. 4. [Baranovskaya L.I., Tsvetkova T. G., Kravets I. A., Lyapunova N. A. Vyyavlenie aktivnykh i repressirovannykh kopii ribosomnogo gena v individual'nykh yadryshkoobrazuyushchikh raionakh khromosom. II Vses. konf. «Genom cheloveka». 1991. P.4 (In Russ.)]
  14. Hungerford P.A. Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Techn. 1965; 40:333–338.
  15. Дружинин В.Г., Ахматьянова В.Р., Головина Т.А. и др. Чувствительность генома и особенности проявления генотоксических эффектов у детей–подростков, подвергающихся воздействию радона в условиях проживания и обучения // Радиационная биология, радиоэкология. – 2009. – Т.49, №5. – c. 568–573. [Druzhinin V.G., Akhmat'yanova V.R., Golovina T.A. i dr. Chuvstvitel'nost' genoma i osobennosti proyavleniya genotoksicheskikh effektov u detei–podrostkov, podvergayushchikhsya vozdeistviyu radona v usloviyakh prozhivaniya i obucheniya. Radiatsionnaya biologiya, radioekologiya. 2009; 49 (5):568-573. (In Russ.)]
  16. Minina V., Sinitsky M., Druzhinin V. et al. Chromosome aberrations in peripheral blood lymphocytes of lung cancer patients exposed to radon and air pollution. Eur. J. Cancer Prev. 2016; (1). doi: 10.1097/CEJ.0000000000000270.
  17. Howell W.M., Black DA. Controlled silver-staining of nucleolus organizer regions with a protective colloidal developer: a1-step method. Experientia. 1980; 36:1014 – 1015.
  18. Бочков Н.П. Хромосомы человека и облучение. – М.: Атомиздат, 1971. [Bochkov N.P. Khromosomy cheloveka i obluchenie. Moscow: Atomizdat; 1971. (In Russ.)]
  19. Ляпунова Н.А. Рибосомные гены в геноме человека: вклад в генетическую индивидуальность и фенотипической проявление дозы гена // Вестн. Рос. АМН. – 2000. - №5. – С. 19 – 23. [Lyapunova N.A. Ribosomnye geny v genome cheloveka: vklad v geneticheskuyu individual'nost' i fenotipicheskoi proyavlenie dozy gena. Vestn. Ros. AMN. 2000; (5):19-23. (In Russ.)]
  20. Дружинин В.Г., Волков А.Н., Глушков А.Н. и др. Роль полиморфизмов генов репарации в оценке чувствительности генома человека к воздействию сверхнормативных концентраций радона // Гигиена и санитария. – 2011. - №5. –С. 26 – 30. [Druzhinin V.G., Volkov A.N., Glushkov A.N. i dr. Role of repair gene polymorphism in estimating the sensitivity of human genome to excess radon concentrations. Gig Sanit. 2011; (5):26-30. (In Russ.)]
  21. Bilban M., Vaupoti J. Chromosome aberrations study of pupils in high radon level elementary school. Health Phys. 2001; 80(2):157–163.
  22. Минина В.И. Гигиенические аспекты формирования хромосомных аберраций у рабочих коксохимического производства: автореферат дис. ...кандидата биологических наук. – Кемерово; 2000. [Minina V.I. Gigienicheskie aspekty formirovaniya khromosomnykh aberratsii u rabochikh koksokhimicheskogo proizvodstva. [avtoreferat dis.] Kemerovo; 2000. (In Russ.)]
  23. Викторова Т.В., Хуснутдинова Э.К., Викторов В.В. и др. Анализ хромосомных аберраций и ядрышкообразующих районов хромосом у рабочих производства пиромеллитового диангидрида: О возможной адаптивной роли вариантов Ag-ЯОР // Генетика. – 1994. – Т. 30, №7. – С. 992 – 998. [Viktorova T.V., Khusnutdinova E.K., Viktorov V.V. i dr. Analiz khromosomnykh aberratsii i yadryshkoobrazuyushchikh raionov khromosom u rabochikh proizvodstva piromellitovogo diangidrida: O vozmozhnoi adaptivnoi roli variantov Ag-YaOR. Russian Journal of Genetics. 1994; 30 (7):992-998. (In Russ.)]
  24. Минина В.И., Дружинин В.Г. Геномные дозы активных генов рРНК у рабочих коксохимического производства // Генетика. – 2004. – Т.40, №12. – С.1702 – 1708. [Minina V.I., Druzhinin V.G. Genomic dosages of active rRNA genes in coke-oven workers. Russian Journal of Genetics. 2004; 40 (12): 1702-1708. (In Russ.)]
  25. Амелина И.В., Медведев И.Н. Частота хромосомных аберраций и активность ядрышкообразующих районов хромосом у человека // Фундаментальные исследования. – 2007. - №1. – С. 33-35. [Amelina I.V., Medvedev I.N. Chastota khromosomnykh aberratsii i aktivnost' yadryshkoobrazuyushchikh raionov khromosom u cheloveka. Fundamental'nye issledovaniya. 2007; (1):33-35. (In Russ.)]
  26. Ляпунова Н.А., Вейко Н.Н. Рибосомные гены в геноме человека: структурно-функциональная организация, фенотипическое проявление и связь с патологией //Генетика в XXI веке: современное состояние и перспектива развития. – 2004. – Т.2 – С.12. [Lyapunova N.A., Veiko N.N. Ribosomnye geny v genome cheloveka: strukturno-funktsional'naya organizatsiya, fenotipicheskoe proyavlenie i svyaz' s patologiei. Genetika v XXI veke: sovremennoe sostoyanie i perspektiva razvitiya. 2004; 12: 12. (In Russ.)]
  27. Минина В.И., Дружинин В.Г., Лунина А.А. и др. Исследование взаимосвязи между полиморфизмом генов репарации ДНК и частотой хромосомных аберраций в лимфоцитах крови человека // Экологическая генетика.- 2011.- Т.IX., №2. – С.74-79. [Minina V.I., Druzhinin V.G., Lunina A.A. et al. Association of DNA repair gene polymorphism with chromosomal aberrations in the human lymphocytes. Ecological genetics. 2011; 9 (2):74-79. (In Russ.)]
  28. Larionov A., Sinitsky M., Druzhinin Vet al. DNA excision repair and double-strand break repair gene polymorphisms and the level of chromosome aberration in children with long-term exposure to radon. International Journal of Radiation Biology. 2016; (1):1 – 9

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. The results of measurements of average specific volume radon activity residential and educational areas of Tashtagol boarding school and control settlements (*p < 0,01; significantly different from control groups values)

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3. Fig. 2. Single fragments frequency in children and adolescents of Russian ethnicity from Tashtagol with different doses of active ribosomal genes (*p < 0,03, significantly difference between children with a medium dose of AcRG from children with a low dose of AcRG)

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Copyright (c) 2017 Timofeeva A.A., Minina V.I., Druzhinin V.G., Golovina T.A., Tolochko T.A., Larionov A.V.

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