LINE-1 methylation index correlates with sister chromatid exchanges and chromatid but not chromosome aberrations in personnel from a nuclear chemical facility with incorporated plutonium-239

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The level of chromosomal abnormalities in the somatic cells of adult individuals is characterized by significant interindividual variability, which may be partly affected by the genetic and epigenetic background. The epigenetic landscape in cells is largely determined by genome methylation. This study aimed to analyse the relationships between global genome methylation and the frequencies of chromosome abnormalities in lymphocytes of plutonium workers. The frequencies of chromosome aberrations, micronuclei, aneuploidy of chromosomes 2, 7, 8, 12, X and Y and sister chromatid exchanges were analysed in the lymphocytes of 40 male workers from a nuclear chemical facility (Seversk, Russia) with incorporated plutonium-239 and 49 healthy male volunteers who had no occupational exposure to ionizing radiation. The long interspersed nuclear elements-1 (LINE-1) methylation index was assessed as a well-known marker of global genome methylation. The frequencies of centromere-negative micronuclei (4.74 ± 2.26‰ vs. 3.02 ± 1.69‰), chromosome-type aberrations (0.81 ± 0.79 vs. 0.44 ± 0.69%) and total chromosome non-disjunction (0.93 ± 0.43 vs. 0.50 ± 0.25%) were significantly higher in the group of workers than in controls (p < 0.05). The LINE-1 methylation index did not differ significantly between the worker and control groups (74.93 ± 3.63 vs. 73.92 ± 4.62%). Correlations between LINE-1 methylation and the frequency of micronuclei (R = –0.35, p = 0.031) were observed in the control group, whereas correlations of LINE-1 methylation with chromatid-type aberrations (R = –0.42, p = 0.012) (but not chromosome-type aberrations) and with sister chromatid exchanges (R = –0.53, p = 0.004) were observed only in the group of plutonium workers. Thus, LINE-1 hypomethylation after plutonium exposure is associated mainly with chromatid breaks, either repaired or misrepaired.

Full Text

Restricted Access

About the authors

S. A. Vasilyev

Tomsk National Research Medical Center of the Russian Academy of Sciences

Author for correspondence.
Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050

E. N. Tolmacheva

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050

E. A. Sazhenova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050

N. N. Sukhanova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050

Yu. S. Yakovleva

Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University

Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050; Tomsk, 634050

N. B. Torkhova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050

M. B. Plaksin

Seversk Clinical Hospital, Siberian Federal Clinical Center of the Federal Biomedical Agency

Email: stanislav.vasilyev@medgenetics.ru
Russian Federation, Seversk, 636035

I. N. Lebedev

Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University

Email: stanislav.vasilyev@medgenetics.ru

Research Institute of Medical Genetics

Russian Federation, Tomsk, 634050; 634050, Tomsk

References

  1. Allshire R.C., Madhani H.D. Ten principles of heterochromatin formation and function // Nat. Rev. Mol. Cell. Biol. 2017. V. 19. № 4. P. 229–244. https://doi.org/10.1038/nrm.2017.119
  2. Ostertag E.M., Kazazian H.H., Jr. Biology of mammalian L1 retrotransposons // Annu. Rev. Genet. 2001. V. 35. №. P. 501–538. https://doi.org/10.1146/annurev.genet.35.102401.091032
  3. Lu K.P., Ramos K.S. Identification of genes differentially expressed in vascular smooth muscle cells following benzo[a]pyrene challenge: Implications for chemical atherogenesis // Biochem. Biophys. Res. Commun. 1998. V. 253. № 3. P. 828–833. https://doi.org/S0006-291X(98)99866-7
  4. Lu K.P., Ramos K.S. Redox regulation of a novel L1Md-A2 retrotransposon in vascular smooth muscle cells // J. Biol. Chem. 2003. V. 278. № 30. P. 28201–28209. https://doi.org/10.1074/jbc.M303888200
  5. Lu K.P., Hallberg L.M., Tomlinson J. et al. Benzo(a)pyrene activates L1Md retrotransposon and inhibits DNA repair in vascular smooth muscle cells // Mutat. Res. 2000. V. 454. № 1–2. P. 35–44. https://doi.org/S0027-5107(00)00095-6
  6. Farkash E.A., Kao G.D., Horman S.R. et al. Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay // Nucl. Ac. Res. 2006. V. 34. № 4. P. 1196–1204. https://doi.org/34/4/1196
  7. Stribinskis V., and Ramos K.S. Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen // Cancer Res. 2006. V. 66. № 5. P. 2616–2620. https://doi.org/66/5/2616
  8. Teneng I., Stribinskis V., Ramos K.S. Context-specific regulation of LINE-1 // Genes Cells. 2007. V. 12. № 10. P. 1101–1110. https://doi.org/GTC1117
  9. Wright R.O., Schwartz J., Wright R.J. et al. Biomarkers of lead exposure and DNA methylation within retrotransposons // Environ. Health. Perspect. 2010. V. 118. № 6. P. 790-795. https://doi.org/10.1289/ehp.0901429
  10. DʹUrso A., Brickner J.H. Mechanisms of epigenetic memory // Trends Genet. 2014. V. 30. № 6. P. 230–236. https://doi.org/10.1016/j.tig.2014.04.004
  11. Vasilyev S.A., Timoshevsky V.A., Lebedev I.N. Cytogenetic mechanisms of aneuploidy in somatic cells of chemonuclear industry professionals with incorporated plutonium-239 // Rus. J. of Genet. 2010. V. 46. № 11. P. 381–1385. https://doi.org/10.1134/s1022795410110141
  12. Muller S., Neusser M., Kohler D. et al. Preparation of complex DNA probe sets for 3D FISH with up to six different fluorochromes // CSH Protoc. 2007. V. 2007. https://doi.org/10.1101/pdb.prot4730
  13. Pembrey M., Golding J., Connelly J. ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis // Eur. J. Hum. Genet. 2015. V. 23. № 9. https://doi.org/10.1038/ejhg.2014.262
  14. Brandom W.F., McGavran L., Bistline R.W. et al. Sister chromatid exchanges and chromosome aberration frequencies in plutonium workers // Int. J. Radiat. Biol. 1990. V. 58. № 1. P. 195–207. https://doi.org/352K8BG4CLW1K5PW
  15. Tawn E.J., Whitehouse C.A., Tarone R.E. FISH chromosome aberration analysis on retired radiation workers from the Sellafield nuclear facility // Radiat. Res. 2004. V. 162. № 3. P. 249–256.
  16. Tawn E.J., Whitehouse C.A., Riddell A.E. FISH chromosome analysis of plutonium workers from the Sellafield nuclear facility // Radiat. Res. 2006. V. 165. № 5. P. 592–597. https://doi.org/RR3530
  17. Hande M.P., Azizova T.V., Burak L.E. et al. Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: An mFISH study // Genes Chrom. Cancer. 2005. V. 44. № 1. P. 1–9. https://doi.org/10.1002/gcc.20217
  18. Anderson R.M., Tsepenko V.V., Gasteva G.N. et al. mFISH analysis reveals complexity of chromosome aberrations in individuals occupationally exposed to internal plutonium: A pilot study to assess the relevance of complex aberrations as biomarkers of exposure to high-LET alpha particles // Radiat. Res. 2005. V. 163. № 1. P. 26–35. https://doi.org/RR3286
  19. Kuzminov A. DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination // Proc. Natl Acad. Sci. USA. 2001. V. 98. № 15. P. 8461–8468. https://doi.org/10.1073/pnas.151260698
  20. Li H., Hilmarsen H.T., Hossain M.B. et al. Telomere length and LINE-1 methylation is associated with chromosomal aberrations in peripheral blood // Genes Chrom. Cancer. 2013. V. 52. № 1. P. 1–10. https://doi.org/10.1002/gcc.22000
  21. Lee Y., Kim Y.J., Choi Y.J. et al. Radiation-induced changes in DNA methylation and their relationship to chromosome aberrations in nuclear power plant workers // Int. J. Radiat. Biol. 2015. V. 91. № 2. P. 142–149. https://doi.org/10.3109/09553002.2015.969847
  22. Chambers J.C., and Taylor J.H. Induction of sister chromatid exchanges by 5-fluorodeoxycytidine: Correlation with DNA methylation // Chromosoma. 1982. V. 85. № 5. P. 603–609.
  23. Hori T.A. Induction of chromosome decondensation, sister-chromatid exchanges and endoreduplications by 5-azacytidine, an inhibitor of DNA methylation // Mutat. Res. 1983. V. 121. № 1. P. 47–52.
  24. Ikushima T. SCE and DNA methylation // Basic Life Sci. 1984. V. 29. Pt. A. P. 161–172.
  25. Lavia P., Ferraro M., Micheli A. et al. Effect of 5-azacytidine (5-azaC) on the induction of chromatid aberrations (CA) and sister-chromatid exchanges (SCE) // Mutat. Res. 1985. V. 149. № 3. P. 463–467.
  26. Shipley J., Sakai K., Tantravahi U. et al. Correspondence between effects of 5-azacytidine on SCE formation, cell cycling and DNA methylation in Chinese hamster cells // Mutat. Res. 1985. V. 150. № 1–2. P. 333–345.
  27. Bianchi N.O., Larramendy M., and Bianchi M.S. The asymmetric methylation of CG palindromic dinucleotides increases sister-chromatid exchanges // Mutat. Res. 1988. V. 197. № 1. P. 151–156.
  28. Albanesi T., Polani S., Cozzi R. et al. DNA strand methylation and sister chromatid exchanges in mammalian cells in vitro // Mutat. Res. 1999. V. 429. № 2. P. 239–248.
  29. Orta M.L., Calderon-Montano J.M., Dominguez I. et al. 5-Aza-2ʹ-deoxycytidine causes replication lesions that require Fanconi anemia-dependent homologous recombination for repair // Nucl. Ac. Res. 2013. V. 41. № 11. P. 5827–5836. https://doi.org/10.1093/nar/gkt270
  30. Osipov A.N., Grekhova A., Pustovalova M. et al. Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation // Oncotarget. 2015. V. 6. № 29. P. 26876–26885. https://doi.org/10.18632/oncotarget.4946
  31. Gundy S., Varga L., Bender M.A. Sister chromatid exchange frequency in human lymphocytes exposed to ionizing radiation in vivo and in vitro // Radiat. Res. 1984. V. 100. № 1. P. 47–54.
  32. Shubber E.K., al-Shaikhly A.W. Cytogenetic analysis of blood lymphocytes from X-ray radiographers // Int. Arch. Occup. Environ. Health. 1989. V. 61. № 6. P. 385–389.
  33. al-Sabti K., Lloyd D.C., Edwards A.A. et al. A survey of lymphocyte chromosomal damage in Slovenian workers exposed to occupational clastogens // Mutat. Res. 1992. V. 280. № 3. P. 215–223.
  34. Bozkurt G., Yuksel M., Karabogaz G. et al. Sister chromatid exchanges in lymphocytes of nuclear medicine physicians // Mutat. Res. 2003. V. 535. № 2. P. 205–213.
  35. Santovito A., Cervella P., Delpero M. Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations // Environ. Toxicol. Pharmacol. 2014. V. 37. № 1. P. 396–403. https://doi.org/10.1016/j.etap.2013.12.009
  36. Geard C.R. Induction of sister chromatid exchange as a function of charged-particle linear energy transfer // Radiat. Res. 1993. V. 134. № 2. P. 187–192.
  37. Schmid E., Roos H. Dose dependence of sister chromatid exchanges in humans lymphocytes induced by in vitro alpha-particle irradiation // Radiat. Environ. Biophys. 1996. V. 35. № 4. P. 311–314.
  38. Cho Y.H., Woo H.D., Jang Y. et al. The association of LINE-1 hypomethylation with age and centromere positive micronuclei in human lymphocytes // PLoS One. 2015. V. 10. № 7. https://doi.org/10.1371/journal.pone.0133909

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Correlations between the LINE-1 methylation index and the frequencies of chromatid and chromosomal aberrations, the level of sister chromatid exchanges and the frequency of micronuclei in the control group (a, c, d, g) and the group of radiochemical workers (b, d, e, z).

Download (371KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences