Molecular genetic markers of sensitivity to industrial environment factors at miners

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Abstract

Background. Active ribosomal genes and DNA repair genes play an important role in restoring genome integrity. Therefore we were studied relationship of active ribosomal genes dose and DNA repair genes polymorphisms with high level of chromosomal disorders in miners.

Materials and methods. The DNA damage level was assessed using chromosomal aberrations (CA) at 288 coal miners and 676 men in the control group. The dose of active ribosomal gene (AcRG) has been analyzed using Ag-NORS staining regions of chromosomes and cytogenetic semi-quantitative evaluation method. Real-time PCR and allele-specific PCR techniques were used to analyze polymorphic variants of the XPG (rs17655), XPD (rs13181), XRCC2 (rs3218536), and XRCC3 (rs861539) genes.

Results. A statistically significant (p = 0.0001) increase of the СА level at miners was found in comparison with the control group. The association XPD 2251T>G locus with increasing CA level is revealed of in recessive inheritance model (padj = 0.0001). The association XPG 3310G>C locus with increasing СА level is revealed at the smoking workers (padj = 0.017). An average dose of AcRG was registered a statistically significant increase in the frequency of single fragments (p = 0.016) at the miners.

Conclusion. The obtained data on associations of chromosomal aberrations with different variants of DNA repair genes and the dose of active ribosomal genes are useful for the formation of high-risk groups.

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About the authors

Anna A. Timofeeva

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

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

Leading Engineer-technologist of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Varvara I. Minina

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

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

Doctor of Biological Sciences, Chief Researcher Laboratory of Cytogenetics

Russian Federation, Kemerovo

Evgeniya A. Astaf’eva

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

Email: astafeva.evgenia@yandex.ru
ORCID iD: 0000-0002-5841-6311
SPIN-code: 9814-4382

Engineer-technologist of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Tatyana A. Golovina

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

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

Engineer-technologist of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Vladislav I. Fedoseev

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

Email: fedoseev.vlig@gmail.com
ORCID iD: 0000-0002-5359-3845
SPIN-code: 1473-4062

engineer-technologist of the cytogenetics laboratory

Russian Federation, Kemerovo

Anastasiya V. Ryzhkova

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

Email: kotia1490@mail.ru
ORCID iD: 0000-0001-5643-5001
SPIN-code: 5666-2145

Leading Engineer-technologist of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Olga A. Soboleva

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

Email: soboleva.olga88@yandex.ru
ORCID iD: 0000-0001-7183-6647
SPIN-code: 6089-2499

Leading Engineer-technologist of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Yana A. Savchenko

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

Email: yasavchenko@ya.ru
ORCID iD: 0000-0003-0754-306X
SPIN-code: 3783-7268

PhD, Senior Researcher of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Marina L. Bakanova

The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences

Email: mari-bakano@ya.ru
ORCID iD: 0000-0002-1238-2427
SPIN-code: 3049-1531

Junior Researcher of the Cytogenetics Laboratory

Russian Federation, Kemerovo

Anton A. Glushkov

Novosibirsk State University

Email: glushkov.anton2404@gmail.com
ORCID iD: 0000-0001-6864-2577
SPIN-code: 5155-1374

Student of the Institute of Medicine and Psychology V. Zelman

Russian Federation, Novosibirsk

References

  1. Бочков Н.П., Пузырев В.П., Смирнихина С.А. Клиническая генетика: учебник / под ред. Н.П. Бочкова. 4-е изд., доп. и перераб. – М.: ГЭОТАР-Медиа, 2015. – 592 с. [Bochkov NP, Puzyrev VP, Smirnikhina SA. Klinicheskaya genetika: uchebnik. Ed. by N.P. Bochkov. 4th revised and updated. Moscow: GEOTAR-Media; 2015. 592 p. (In Russ.)]
  2. Мун С.А., Ларин С.А., Глушков А.Н. Влияние роста добычи угля на загрязнение атмосферы и заболеваемость раком легкого в Кемеровской области // Современные проблемы науки и образования. – 2013. – № 1. – С. 69. [Mun SA, Larin SA, Glushkov AN. The influence of mining on atmosphere contamination and lung cancer in the kemerovo region. Sovremennye problemy nauki i obrazovaniya. 2013;(1):69. (In Russ.)]
  3. Мун С.А., Глушков А.Н. Расчет прогнозов заболеваемости раком легкого у мужчин в связи с техногенным загрязнением атмосферы в Кемеровской области // Гигиена и санитария. – 2014. – T. 93. – № 2. – С. 37–40. [Mun SA, Glushkov AN. Calculation of prognoses of lung cancer in males from technogenic contamination of atmosphere in the Kemerovo region. Gig Sanit. 2014;93(2):37-40. (In Russ).]
  4. Guerrero-Castilla A, Olivero-Verbel J, Marrugo-Negrete J. Heavy metals in wild house mice from coal-mining areas of Colombia and expression of genes related to oxidative stress, DNA damage and exposure to metals. Mutat Res Genet Toxicol Environ Mutagen. 2014; 762:24-29. https://doi.org/10.1016/j.mrgentox.2013.12.005.
  5. Rohr P, Kvitko K, da Silva FR, et al. Genetic and oxidative damage of peripheral blood lymphocytes in workers with occupational exposure to coal. Mutat Res. 2013;758(1-2):23-28. https://doi.org/10.1016/j.mrgentox.2013.08.006.
  6. León-Mejía G, Quintana M, Debastiani R, et al. Genetic damage in coal miners evaluated by buccal micronucleus cytome assay. Ecotoxicol Environ Saf. 2014;107:133-139. https://doi.org/10.1016/j.ecoenv.2014.05.023.
  7. Kloosterman WP, Hochstenbach R. Deciphering the pathogenic consequences of chromosomal aberrations in human genetic disease. Mol Cytogenet. 2014;7(1):100-112. https://doi.org/10.1186/s13039-014-0100-9.
  8. Ensminger M, Iloff L, Ebel C, et al. DNA breaks and chromosomal aberrations arise when replication meets base excision repair. J Cell Biol. 2014;206(1):29-43. https://doi.org/10.1083/jcb.201312078.
  9. Sugasawa K. Regulation of damage recognition in mammalian global genomic nucleotide excision repair. Mutat Res. 2010;685(1-2):29-37. https://doi.org/10.1016/j.mrfmmm.2009.08.004.
  10. Lindström MS, Jurada D, Bursac S, et al. Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis. Oncogene. 2018;37(18):2351-2366. https://doi.org/10.1038/s41388-017-0121-z.
  11. Weeks SE, Metge BJ, Samant RS. The nucleolus: a central response hub for the stressors that drive cancer progression. Cell Mol Life Sci. 2019;76(22):4511-4524. https://doi.org/10.1007/s00018-019-03231-0.
  12. Wang J, Zhang ZQ, Li FQ, et al. Triptolide interrupts rRNA synthesis and induces the RPL23MDM2p53 pathway to repress lung cancer cells. Oncol Rep. 2020;43(6):1863-1874. https://doi.org/10.3892/or.2020.7569.
  13. McStay B. Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination. Genes Dev. 2016;30(14):1598-1610. https://doi.org/ 10.1101/gad.283838.116.
  14. Ляпунова Н.А., Вейко Н.Н. Рибосомные гены в геноме человека: идентификация четырех фракций, их организация в ядрышке и метафазных хромосомах // Генетика. – 2010. – Т. 46. – № 9. – С. 1205–1209. [Lyapunova NA, Veiko NN. Ribosomal genes in the human genome: identification of four fractions, their organization in the nucleolus and metaphase chromosomes. Russian Journal of Genetics. 2010;46(9):1205-1209. (In Russ.)]. https://doi.org/10.1134/S1022795410090140.
  15. Paredes S, Branco AT, Hartl DL, et al. Ribosomal DNA deletions modulate genome-wide gene expression: “rDNA-Sensitive” genes and natural variation. PLoS Genetics. 2011;7(4): e1001376. https://doi.org/10.1371/journal.pgen. 1001376.
  16. Ляпунова Н.А., Пороховник Л.Н., Косякова Н.В., и др. Жизнеспособность носителей хромосомных аномалий зависит от геномной дозы активных рибосомных генов (генов рРНК) // Генетика. –2017. – Т. 53. – № 6. – С. 722–731. [Lyapunova NA, Porokhovnik LN, Kosyakova NV, et al. 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.)]. https://doi.org/10.7868/S0016675817060091.
  17. Мамаев Н.Н. Структурная организация и экспрессия рибосомных генов в физиологических и патологических условиях // Цитология. – 1997. – № 1. – С. 80–83. [Mamaev NN. Strukturnaya organizaciya i ekspressiya ribosomnyh genov v fiziologicheskih i patologicheskih usloviyah. Cell and Tissue Biology. 1997;(1): 80-83. (In Russ.)]
  18. Туганова Т.Н., Болгова Л.С., Махортова Н.Г., Алексеенко О.И. Диагностический алгоритм цитологического исследования фиброаденом и рака молочной железы // Онкология. – 2007. – Т. 9. – № 4. – С. 315–320. [Tuganova TN, Bolgova LS, Mahortova NG, Alekseenko OI. Diagnostic algorithm of cytologic examination of fibroadenomas and breast cancer. Oncology. 2007;9(4):315-320. (In Russ.)]
  19. Derenzini M, Trere D, O’Donohue M-F, Ploton D. Interphase nucleolar organiser regions in tumour pathology. Chapter 7. In: Crocker J, Murray PG, ed. Molecular biology in cellular pathology. John Wiley & Sons, Ltd.; 2003. Р. 137-152. https://doi.org/10.1002/0470867949.ch7.
  20. Frankowski KJ, Wang C, Patnaik S, et al. Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Sci Transl Med. 2018;10(441): eaap8307. https://doi.org/10. 1126/scitranslmed.aap8307.
  21. Kanis MJ, Qiang W, Pineda M, et al. A small molecule inhibitor of the perinucleolar compartment, ML246, attenuates growth and spread of ovarian cancer. Gynecol Oncol Res Pract. 2018;5(7):1-9. https://doi.org/10.1186/s40661-018-0064-2.
  22. Вейко Н.Н., Терехов С.М., Шубаева Н.О., и др. «Ранний» и «поздний» ответ культивируемых фибробластов кожи здоровых доноров и больных ревматоидным артритом на окислительный стресс. Взаимосвязь между интенсивностью гибели клеток и количеством активных копий рибосомных генов // Молекулярная биология. – 2005. – Т. 39. – № 2. – С. 264–275. [Veiko NN, Terekhov SM, Shubaeva NO, et al. Vzaimosvyaz’ mezhdu intensivnost’yu gibeli kletok i kolichestvom aktivnykh kopiy ribosomnykh genov. Molecular Biology. 2005;39(2):264-275. (In Russ.)]
  23. Porokhovnik LN, Passekov VP, Gorbachevskaya NL, et al. Active ribosomal genes, translational homeostasis and oxidative stress in the pathogenesis of schizophrenia and autism. Psychiatr Genet. 2015;25(2):79-87. https://doi.org/10.1097/ypg.0000000000000076.
  24. Hungerford PA. Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Techn. 1965;40(6):333-338. https://doi.org/10.3109/10520296509116440.
  25. 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;27(1):6-12. https://doi.org/10.1097/CEJ. 0000000000000270.
  26. Howell WM, Black DA. Controlled silver-staining of nucleolus organizer regions with a protective colloidal developer: a1-step method. Experientia. 1980;36(8):1014-1015. https://doi.org/ 10.1007/BF01953855.
  27. Moore JH, Gilbert JC, Tsai CT, et al. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol. 2006;241(2):252-261. https://doi.org/10.1016/j.jtbi.2005.11.036.
  28. IGSR: The International Genome Sample Resource. Supporting open human variation data [cited 2020 March 18]. Available from: https://www.internationalgenome.org/.
  29. Ляпунова Н.А., Еголина Н.А., Цветкова Т.Г., и др. Рибосомные гены в геноме человека: вклад в генетическую индивидуальность и фенотипической проявление дозы гена // Вестник РАМН. – 2000. – № 5. – С. 19–23. [Lyapunova NA, Egolina NA, Tsvetkova TG, et al. Ribosomnye geny v genome cheloveka: vklad v geneticheskuyu individual’nost’ i fenotipicheskoy proyavlenie dozy gena. Annals of the Russian Academy of Medical Sciences. 2000;(5):19-23. (In Russ.)]
  30. Волобаев В.П., Синицкий М.Ю., Кулемин Ю.Е. Цитогенетический статус шахтеров угольных шахт с легочными профессиональными заболеваниями и влияние на него аллелей генов XPD и XPG // Экологическая генетика. – 2015. – Т. 13. – № 4. – С. 12–15. [Volobaev VP, Sinitsky MYu, Kulemin YuE. Cytogenetic status in coal-miners with occupational pulmonary diseases and influence the polymorphisms of XPD and XPG genes. Ecological genetics. 2015;13(4):12-15. (In Russ.)]. https://doi.org/org/10.1781/ecogen13412-15.
  31. Harms C, Salama SA, Sierra-Torres CH, et al. Polymorphisms in DNA repair genes, chromosome aberrations and lung cancer. Environ Mol Mutagen. 2004;44(1):74-82. https://doi.org/10.1002/em.20031.
  32. Сальникова Л.Е., Чумаченко А.Г., Веснина И.Н., и др. Полиморфизм генов репарации и цитогенетические эффекты облучения // Радиационная биология. Радиоэкология. –2010. –Т. 50. –№ 6. – С. 656–662. [Sal’nikova LE, Chumachenko AG, Vesnina IN, et al. Polymorphism of repair genes and cytogenetic radiation effects. Radiobiology and Radioecology. 2010;50(6):656-662. (In Russ.)]. https://doi.org/10.1134/s0006350911020266.
  33. Trego Kelly S. Non-catalytic roles for XPG with BRCA1 and BRCA2 in homologous recombination and genome stability. Mol Cell. 2016;61(4):535-546. https://doi.org/10.1016/j.molcel.2015.12.026.
  34. Musak L, Polakova V, Halasova E, et al. Effect of occupational exposure to cytostatics and nucleotide excision repair polymorphism on chromosomal aberrations frequency. Interdiscip Toxicol. 2009;2(1):13-17. https://doi.org/10.2478/v10102-009-0002-6.
  35. Sinitsky MY, Larionov AV, Asanov MA, Druzhinin VG. Associations of DNA-repair gene polymorphisms with a genetic susceptibility to ionizing radiation in residents of areas with high radon (222Rn) concentration. Int J Radiat Biol. 2015;91(6):486-494. https://doi.org/10.3109/09553002.2015.1012306.
  36. Минина В.И., Дружинин В.Г. Геномные дозы активных генов рРНК у рабочих коксохимического производства // Генетика. – 2004. – Т. 40. – № 12. – С. 1702–1708. [Minina VI, Druzhinin VG. Genomic dosages of active rRNA genes in coke-oven workers. Russian Journal of Genetics. 2004;40(12):1702-1708. (In Russ.)]. https://doi.org/10.1007/s11177-005-0074-0.
  37. Тимофеева А.А, Минина В.И., Дружинин В.Г., и др. Цитогенетические эффекты сверхнормативного воздействия радона в зависимости от индивидуальной дозы активных рибосомных генов // Экологическая генетика. –2017. –Т. 15. –№ 4. –С. 33–40. [Timofeeva AA, Minina VI, Druzhinin VG, et al. Cytogenetic effects of excessive radon exposure depending on the individual dosage of active ribosomal genes. Ecological genetics. 2017;15(4):33-40. (In Russ.)]. https://doi.org/10.17816/ecogen15433-40.
  38. 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 TV, Khusnutdinova EK, Viktorov VV, et al. Analiz khromosomnykh aberratsiy i yadryshkoobrazuyushchikh raionov khromosom u rabochikh proizvodstva piromellitovogo diangidrida: o vozmozhnoy adaptivnoy roli variantov Ag-YaOR. Russian Journal of Genetics. 1994;30(7):992-998. (In Russ.)]
  39. Амелина И.В., Медведев И.Н. Частота хромосомных аберраций и активность ядрышкообразующих районов хромосом у человека // Фундаментальные исследования. –2007. –№ 1. –С. 33–35. [Amelina IV, Medvedev IN. Chastota khromosomnykh aberratsiy i aktivnost’ yadryshkoobrazuyushchikh raionov khromosom u cheloveka. Fundamental’nie issledovaniia. 2007;(1):33-35. (In Russ.)]
  40. Grewal SI, Jia ST. Heterochromatin revisited. Nat Rev Genet. 2007;8(1):35-46. https://doi.org/10.1038/nrg2008.
  41. Killen MW, Stults DM, Adachi N, et al. Loss of Bloom syndrome protein destabilizes human gene cluster architecture. Hum Mol Genet. 2009;18(18):3417-3428. https://doi.org/10. 1093/hmg/ddp282.
  42. Hallgren J, Pietrzak M, Rempala G, et al. Neurodegeneration-associated instability of ribosomal DNA. Biochim Biophys Acta. 2014;1842(6): 860-868. https://doi.org/10.1016/j.bbadis.2013. 12.012.
  43. Pietrzak M, Rempala G, Nelson PT, et al. Epigenetic silencing of nucleolar rRNA genes in Alzheimer’s disease. PLoS One. 2011;6(7): e22585. https://doi.org/10.1371/journal.pone. 0022585.
  44. Parlato R, Kreiner G. Nucleolar activity in neurodegenerative diseases: a missing piece of the puzzle? J Mol Med (Berl). 2013;91(5): 541-547. https://doi.org/10.1007/s00109-012-0981-1.
  45. MacLeod RA, Spitzer D, Bar-Am I, et al. Karyotypic dissection of Hodgkin’s disease cell lines reveals ectopic subtelomeres and ribosomal DNA at sites of multiple jumping translocations and genomic amplification. Leukemia. 2000;14(10): 1803-14. https://doi.org/10.1038/sj.leu.2401894.
  46. Ляпунова Н.А., Пороховник Л.Н., Косякова Н.В., и др. Жизнеспособность носителей хромосомных аномалий зависит от геномной дозы активных рибосомных генов (генов рРНК) // Генетика. – 2017. – Т. 53. – № 6. – С. 722–731. [Lyapunova NA, Porokhovnik LN, Kosyakova NV, et al. 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.)]. https://doi.org/10.7868/S0016675817060091.

Supplementary files

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2. Figure: 1. Frequency of single chromosome fragments in miners with different doses of active ribosomal genes (AcRG). * p = 0.016, difference from miners with a low dose of AcRG

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3. Figure: 2. Frequency of chromosomal aberrations depending on the XPD gene polymorphism and the dose of active ribosomal genes

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4. Figure: 3. Cluster analysis of intergenic interactions in the formation of chromosomal abnormalities in the general sample of miners. Short lines indicate strong interplay of gene loci; long - for a weak connection; light gray and dark gray - duplication of effects between loci

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Copyright (c) 2020 Timofeeva A.A., Minina V.I., Astaf’eva E.A., Golovina T.A., Fedoseev V.I., Ryzhkova A.V., Soboleva O.A., Savchenko Y.A., Bakanova M.L., Glushkov A.A.

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