Monitoring of cytogenetic instability by micronuclei assay of both immunocompetent and non-immunocompetent cells in tick-borne encephalitis patients depending on variants of glutathione-S-transferase genes in the genotype

Cover Page


Cite item

Full Text

Abstract

Aim of this study was to study the dynamics of the frequency of cytokinesis-blocked T-lymphocytes with micronuclei in peripheral blood and the frequency of buccal micronucleated epithelium cells for a period of half a year in patients with acute tick-borne encephalitis, depending on burden of active and inactive variants of glutathione-S-transferase genes (GSTM1 and GSTT1) in the patient's genotype. We carried out micronucleus assay in immunocompetent and non-immunocompetent cells in 54 patients with acute tick-borne encephalitis and 35 healthy persons (control) residing in the Tomsk and Tyumen regions. To analyze the frequency of cytokinesis-blocked micronucleated T-lymphocytes was used venous peripheral blood as material for phytohemagglutinin-stimulated cultures, and to study the frequency of buccal micronucleated cells, samples of the buccal mucous membrane epithelial cells were obtained. To carried out both techniques of micronucleus assay, cytological preparations were prepared, which were stained using the Giemsa or Felgen methods. The material for the study was obtained repeatedly during admission of patients to treatment, and also after 1 week, 1, 3 and 6 months.  Polymerase chain reaction was used to analyze the alleles of the GSTM1 and GSTT1 genes. As a result of this analysis was found a significant increase in the frequency of micronucleated cells in tick-borne encephalitis patients compared with the control group. In addition, the frequency of cytokinesis-blocked micronucleated T-lymphocytes was increased significantly higher than the one of micronucleated buccal cells. The most significant and prolonged increase in the frequency of micronucleated cells was associated with the mutant inactive variants of the genes GSTM1 (0/0) and GSTT1 (0/0). In the patients with burden the inactive forms of these genes, the cytogenetic instability of the cytokinesis-blocked blood T-lymphocytes could persist for up to six months. In case of buccal cells, the frequency of micronucleated cells was close to the one in the control group as early as 1-3 months after a course of treatment. Conclusion. It was found that the most increased and prolonged frequency of cytogenetically instable cells persisted in cytokinesis-blocked T-lymphocytes of peripheral blood of patients with tick-borne encephalitis who were carriers of the genotype with inactive variants of  both GSTM1 (0/0) and GSTT1 (0/0 ) glutathione-S-transferase genes.

About the authors

Nikolay Nikolaevich Ilyinskikh

Siberian State Medical University, National Research Tomsk State University

Author for correspondence.
Email: nauka-tomsk@yandex.ru
ORCID iD: 0000-0003-1014-1096

PhD, Doctor of Biological Sciences, Professor, Professor of Department of Biology and Genetics, Siberian State Medical University, Professor of Department of Ecology, Nature Management and Environmental Engineering, National Research Tomsk State University

Russian Federation

Ekaterina Nikolaevna Ilyinskikh

Siberian State Medical University, National Research Tomsk State University

Email: infconf2009@mail.ru
ORCID iD: 0000-0001-7646-6905
PhD, MD, Associate Professor, Professor of Department of Infectious Diseases and Epidemiology, Siberian State Medical University, Professor of Department of Ecology, Nature Management and Environmental Engineering, National Research Tomsk State University Russian Federation

Evgenia Vladimirovna Zamyatina

Siberian State Medical University

Email: e_zamyt@mail.ru
ORCID iD: 0000-0001-7579-8975

Assistant of Department of Infectious Diseases and Epidemiology, Siberian State Medical University

Russian Federation

Svetoslava Vyacheslavovna Lee

Siberian State Medical University

Email: infconf2009@mail.ru

5th year student of the Pediatric faculty, Siberian State Medical University

Russian Federation

References

  1. Zaharicheva T.A.1, Koval'skii Yu. G.1, Lebed'ko O.A.2, Mzhel'skaya T.V. Oxidative stress in patients with tick-borne encephalitis in the Far East of The Russian Federation. Dal'nevostochnyj zhurnal infekcionnoj patologii (Far Eastern Journal of Infectious Pathology), 2012, vol. 20, no. 8, pp. 41-45. (In Russ.). URL: https://elibrary.ru/item.asp?id=17995983
  2. Il'inskih I.N., Novickij V.V., Il'inskih E.N., Il'inskih N.N., Tkachenko S.B. Infectious karyopathology. Tomsk: Tomskij gosudarstvennyj universitet (Tomsk State University), 2005. 168 p. (In Russ.). URL: https://elibrary.ru/item.asp?id=20162195
  3. Il'inskih N.N., Vasil'ev S.A., Kravcov V.Ju. Micronuclear test in screening and monitoring of mutagens. Saarbrucken (Deutschland): LAP LAMBERT Academic Publishen. GmbH&Co.KG., 2011, 216 p. URL: https://elibrary.ru/item.asp?id=19690099
  4. Legotkin, A.N., Lopatina A.B. Study of genes of GSTP1, GSTT1, GSTM1 // Uspehi sovremennoj nauki (Successes of contemporary science), 2016, vol. 2, no. 9, pp. 23–25. (In Russ.). URL:https://elibrary.ru/item.asp?id=27179502
  5. Stepanova N.A., Kantemirova B.I., Galimzyanov Kh.M. Intoxication syndrome in patients with pulmonary tuberculosis in relation to the system glutathione transferase gene polymorphism. Zhurnal infektologii (Journal Infectology), 2017, vol. 9, no 2, pp. 13–16. (In Russ.). URL:http://journal.niidi.ru/jofin/issue/view/50/showToc [doi: 10.22625/2072-6732-2017-9-2-13-16]
  6. Filippova I.N., Khrunin A.V., Limborska S.A. Analysis of GSTM1 gene deletion in the context of the haplotype diversity of the GSTM genomic cluster in three Russian populations. Molecular Genetics, Microbiology and Virology, 2014, Т. 29, № 2, С. 53-57. (In Russ.). URL:http://www.mgmv.ru/item72/item74/
  7. Hasanova G.M., Valishin D.A., Tutel'jan A.V., Hasanova A.N. Forecasting model of gene enzyme polymorphism detoxification in patients suffered from HFRS// Zhurnal infektologii (Journal Infectology), 2016, vol. 8, no. 1, pp. 73–78. (In Russ.). URL:http://journal.niidi.ru/jofin/issue/view/41/showToc
  8. Bigatti M.P., Santovito A. Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) polymorphisms in a sample of the population in Northern Italy. Genetika, 2007, vol. 43, no. 6, pp. 827–830. (In Russ.). URL: https://elibrary.ru/ item.asp?id=9537075
  9. Board P.G., Menon D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochim. Biophys. Acta, 2013, vol. 1830, no 5, pp. 3267–3288. URL: https://www.sciencedirect.com/science/article/pii/
  10. S030441651200339X?via%3Dihub [doi: 10.1016/j.bbagen.2012.11.019]
  11. Bolognesi C., Fenech M. Micronucleus assay in human cells: lymphocytes and buccal cells. Methods Mol. Biol., 2013, vol. 1044, pp. 191-207. URL: https://link.springer.com/protocol/10.1007%2F978-1-62703-529-3_10 [doi: 10.1007/978-1-62703-529-3_10]
  12. Fenech M., Kirsch-Volders M., Natarajan A.T., Surralles J., Crott J.W., Parry J., Norppa H., Eastmond D.A., Tucker J.D., Thomas P. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis, 2011, vol. 26, pp. 125-132. URL: https://academic.oup.com/mutage/article/26/1/125/1054873 [doi: 10.1093/mutage/geq052]
  13. Fernandes R.C., Hasan M., Gupta H., Geetha K., Rai P.S., Hande M.H., D'Souza S.C., Adhikari P., Brand A., Satyamoorthy K. Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to malaria infection in an Indian population. Mol. Genet. Genomics, 2015, vol. 290, no. 3, pp. 1155-1168. URL: https://link.springer.com/article/10.1007%2Fs00438-014-0984-4 [doi: 10.1007/s00438-014-0984-4]
  14. Hung R.J., Boffetta P., Brockmöller J. Butkiewicz D., Cascorbi I., Clapper M.L., Garte S., Haugen A., Hirvonen A., Anttila S., Kalina I., Le Marchand L., London S.J., Rannug A., Romkes M., Salagovic J., Schoket B., Gaspari L., Taioli E. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis. Carcinogenesis, 2003, vol. 24, no. 5, pp. 875–882. URL:https://academic.oup.com/carcin/article/
  15. /5/875/2390467 [doi.org/10.1093/carcin/bgg026]
  16. Il’inskikh N.N., Il’inskikh I.N. Effect of virus of tick-borne encephalitis virus on the chromosome apparatus of human cells. Tsitol Genet., 1976, vol. 10, no. 4, pp. 331-333. URL: https://www.ncbi.nlm.nih.gov/pubmed/982562
  17. Parsons M., Campa A., Lai S., Li Y., Martinez J.D., Murillo J., Greer P., Martinez S.S., Baum M.K. Effect of GSTM1-polymorphism on disease progression and oxidative stress in HIV infection: modulation by HIV/HCV co-infection and alcohol consumption. J. AIDS Clin. Res., 2013, vol. 4, no. 9, pp. 248-252. URL: https://www.omicsonline.org/effect-of-gstmpolymorphism-on-disease-progression-and-oxidative-stress-in-hiv-infection-modulation-by-hivhcv-coinfection-and-alcohol-consumption-2155-6113.1000237.php?aid=19177 doi: 10.4172/2155-6113.1000237
  18. Priya K., Yadav A., Kumar N., Gulati S., Aggarwal N., Gupta R. Glutathione S-Transferase Gene Polymorphisms: Modulator of Genetic Damage in Gasoline Pump Workers. Int. J. Toxicol., 2015, vol. 34, no. 6, pp. 500-504. URL:http://journals.sagepub.com/doi/abs/10.1177/1091581815603935?journalCode=ijtb [doi: 10.1177/1091581815603935]
  19. Saha S.K., Lee S.B., Won J., Choi H.Y., Kim K., Yang G.M., Dayem A.A., Cho S.G. Correlation between Oxidative Stress, Nutrition, and Cancer Initiation. Int. J. Mol. Sci., 2017, vol. 18, no. 7, e1544. URL: http://www.mdpi.com/1422-0067/18/7/1544 [doi: 10.3390/ijms18071544]
  20. Skjelbred C.F., Svendsen M., Haugan V., Eek A.K., Clausen K.O., Kure E.H., Tuimala J.T., Svendsen M.V., Norppa H., Hansteen I.L. Influence of GSTM1, GSTT1, GSTP1, NAT1, NAT2, EPHX1, MTR and MTHFR polymorphism on chromosomal aberration frequencies in human lymphocytes Carcinogenesis, 2011, vol. 32, no. 3, pp. 399–405. URL: https://academic.oup.com/carcin/article/32/3/399/2463473 [doi: 10.1093/carcin/bgq246]
  21. Zeng Y., Bai J., Deng L.C., Xie Y.P., Zhao F., Huang Y. Association of the Glutathione S-transferase T1 Null Genotype with Risk of Gastric Cancer: a Meta-analysis in Asian Populations. Asian Pac. J. Cancer Prev., 2016, vol. 17, no. 3, pp. 1141–1148. URL: 27039739&key=2016.17.3.1141' target='_blank'>http://journal.waocp.org/?sid=Entrez:PubMed&id=PMID: 27039739&key=2016.17.3.1141

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Ilyinskikh N.N., Ilyinskikh E.N., Zamyatina E.V., Lee S.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies