Skip to main content
Log in

Dependence of the Translocation Frequency in Blood Lymphocytes on the Dose and Age at the Onset of Exposure in Residents of the Techa Riverside Settlements

  • STUDYING THE CONSEQUENCES OF RADIATION ACCIDENTS
  • Published:
Biology Bulletin Aims and scope Submit manuscript

Abstract

Evaluation of age effect on the frequency of radiation-induced translocations, registered using FISH in circulating T-lymphocytes in the long-term period after exposure, is both of theoretical and practical interest for the purposes of biodosimetry. The objective of our study was to analyze the dose dependence of the translocation frequency in the peripheral blood T-lymphocytes in donors of different age who were exposed in the Techa riverside settlements (n = 197). In cytogenetic studies, whole chromosome painting probes were used to stain three pairs of chromosomes. A total of 104 721 genome equivalents (GE) were studied and 2540 translocations were found. For each donor, the individual absorbed doses in organs and tissues at the time of blood sampling were calculated using the Techa River Dosimetry System. In addition, doses to T-lymphocytes and their progenitors were calculated using the innovative modelling approach with due account of age related-dynamics of T-lymphocytes. The age dependence of the translocation frequency was associated particularly with these doses. The main sources of donor exposure were 89,90Sr, accumulating in bones and irradiating the bone marrow almost locally. To assess the parameters of the dose-effect relationship, linear regression model was used. After taking into account background values, the lowest frequency of translocations per 1000 GE per Gy was found in donors aged 0–5 years at the time of exposure (9.3 ± 1.3), which is statistically significantly lower than in children aged 6–18 years (15.3 ± 1.5), but not in adults (11.9 ± 2.9). The value for adults (>18 years) was characterized by the maximum scatter, but was similar to the values obtained in an international study of nuclear enterprise personnel after external exposure (11.6 ± 1.6). The values of the background translocation frequencies registered in various age groups correspond to the published data obtained in a joint international study on unexposed donors. We have also confirmed the absence of sex-effect on the frequency of translocations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Notes

  1. One of the key proteins involved in DSB repair.

  2. The authors did not indicate that they studied T-lymphocytes specifically, but these methods are used specifically for cytogenetic studies of T-lymphocytes.

REFERENCES

  1. Tucker, J.D., Low-dose ionizing radiation and chromosome translocations: a review of the major considerations for human biological dosimetry, Mutat. Res., 2008, vol. 659, no. 3, pp. 211–220. https://doi.org/10.1016/j.mrrev.2008.04.001

    Article  PubMed  CAS  Google Scholar 

  2. Vorobtsova, I., Semenov, A., Timofeyeva, N., et al., An investigation of the age-dependency of chromosome abnormalities in human populations exposed to low-dose ionising radiation, Mech. Ageing Dev., 2001, vol. 122, no. 13, pp. 1373–1382. https://doi.org/10.1016/s0047-6374(01)00275-5

    Article  PubMed  CAS  Google Scholar 

  3. Sigurdson, A.J., Ha, M., Hauptmann, M., Bhatti, P., et al., International study of factors affecting human chromosome translocations, Mutat. Res., 2008, vol. 652, no. 2, pp. 112–121. https://doi.org/10.1016/j.mrgentox.2008.01.005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Rube, C.E., Fricke, A., Widmann, T.A., et al., Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging, PLoS One, 2011, vol. 6, no. 3, p. e17487. https://doi.org/10.1371/journal.pone.0017487

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  5. Tawn, E.J., Curwen, G.B., Jonas, P., et al., Chromosome aberrations determined by FISH in radiation workers from the Sellafield Nuclear Facility, Radiat. Res., 2015, vol. 184, no. 3, pp. 296–303. https://doi.org/10.1667/RR14125.1

    Article  ADS  PubMed  CAS  Google Scholar 

  6. Sotnik, N.V., Osovets, S.V., Scherthan, H., and Azizova, T.V., mFISH analysis of chromosome aberrations in workers occupationally exposed to mixed radiation, Radiat. Environ. Biophys., 2014, vol. 53, no. 2, pp. 347–354. https://doi.org/10.1007/s00411-014-0536-7

    Article  PubMed  CAS  Google Scholar 

  7. Vozilova, A.V., Shagina, N.B., Degteva, M.O., et al., Preliminary FISH-based assessment of external dose for residents exposed on the Techa River, Radiat. Res., 2012, vol. 177, no. 1, pp. 84–91. https://doi.org/10.1667/rr2485.1

    Article  ADS  PubMed  CAS  Google Scholar 

  8. Vozilova, A.V., Shagina, N.B., Degteva, M.O., et al., FISH analysis of translocations induced by chronic exposure to Sr radioisotopes: second set of analysis of the Techa River Cohort, Radiat. Prot. Dosim., 2014, vol. 159, nos. 1–4, pp. 34–37. https://doi.org/10.1093/rpd/ncu131

    Article  CAS  Google Scholar 

  9. Degteva, M.O. Shishkina, E.A., Tolstykh, E.I., et al., Application of the EPR and FISH methods to dose reconstruction for people exposed in the Techa River a-rea, Radiats. Biol. Radioecol., 2017, vol. 57, no. 1, pp. 34–45. PMID: 30698929.

    Google Scholar 

  10. Tolstykh, E.I., Vozilova, A.V., Degteva, M.O., et al., Concept of T-cell genus as the basis for the analysis of FISH results after local bone marrow exposure, Radiats. Biol. Radioecol., 2020, vol. 60, no. 1, pp. 12–25. https://doi.org/10.31857/S0869803121040111

    Article  Google Scholar 

  11. Tolstykh, E.I., Degteva, M.O., Vozilova, A.V., and Anspaugh, L.R., Local bone-marrow exposure: how to interpret the data on stable chromosome aberrations in circulating lymphocytes? (some comments on the use of FISH method for dose reconstruction for Techa riverside Residents), Radiat. Environ. Biophys., 2017, vol. 56, no. 4, pp. 389–403. https://doi.org/10.1007/s00411-017-0712-7

    Article  PubMed  Google Scholar 

  12. Tolstykh, E.I., Degteva, M.O., Vozilova, A.V., and Akleyev, A.V., Approaches to the cytogenetic assessment of the dose due to radiation exposure of the gut associated lymphoid tissue, Radiats. Biol. Radioecol., 2021, vol. 61, no. 4, pp. 339–352. https://doi.org/10.31857/S0869803121040111

    Article  Google Scholar 

  13. Giussani, A., Lopez, M.A., Romm, H., et al., Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications, Radiat. Environ. Biophys., 2020, vol. 59, no. 3, pp. 357–387. https://doi.org/10.1007/s00411-020-00845-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Tolstykh, E.I., Dogteva, M.O., Krivoshchapov, V.A., and Nap’ye, B.A., Method for estimating individual values of 90Sr intake with diet based on dental probe measurements in residents of Techa River coastal villages, Vopr. Radiats. Bezop., 2019, vol. 93, no. 4, pp. 55–63.

    Google Scholar 

  15. Bauchinger, M., Salassidis, K., Braselmann, H., et al., FISH-based analysis of stable translocations in a Techa River population, Int. J. Radiat. Biol., 1998, vol. 73, no. 6, pp. 605–612. https://doi.org/10.1080/095530098141852

    Article  PubMed  CAS  Google Scholar 

  16. Degteva, M.O., Napier, B.A., Tolstykh, E.I., et al., Enhancements in the Techa River dosimetry system: TRDS-2016D code for reconstruction of deterministic estimates of dose from environmental exposures, Health Phys., 2019, vol. 117, no. 4, pp. 378–387. https://doi.org/10.1097/HP.0000000000001067

    Article  PubMed  CAS  Google Scholar 

  17. Degteva, M.O., Shagina, N.B., Vorobiova, M.I., et al., Contemporary understanding of radioactive contamination of the Techa River in 1949–1956, Radiats. Biol. Radioecol., 2016, vol. 56, no. 5, pp. 523–534. PMID: 30703313.https://doi.org/10.7868/S0869803116050039

    Article  PubMed  CAS  Google Scholar 

  18. Bains, I., Mathematical modelling of T cell homeostasis, Ph.D. Thesis, University College, London, 2010. http://discovery.ucl.ac.uk/20159/1/20159.pdf.

  19. Bains, I., Yates, A.J., and Callard, R.E., Heterogeneity in thymic emigrants: implications for thymectomy and immunosenescence, PLoS One, 2013, vol. 8, no. 2, p. e49554. https://doi.org/10.1371/journal.pone.0049554

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  20. Hirosoft. Epicure: Fast, interactive software for the analysis of medical, public health, epidemiologic, econometric, and reliability data V. 2.10, Seattle, WA: Hirosoft International Corporation, 1998.

  21. Tolstykh, E.I., Degteva, M.O., Vozilova, A.V., et al., Interpretation of FISH results in the case of nonuniform internal radiation exposure of human body with the use of model approach, Russ. J. Genet., 2019, vol. 55, no. 10, pp. 1227–1233. https://doi.org/10.1134/S1022795419100132

    Article  CAS  Google Scholar 

  22. Napier, B.A., Degteva, M.O., Shagina, N.B., and Anspaugh, L.R., Uncertainty analysis for the Techa River dosimetry system, Med. Radiol. Radiat. Saf., 2013, vol. 58, pp. 5–28.

    Google Scholar 

  23. Yates, A., Chan, C.C., Callard, R.E., et al., An approach to modelling in immunology, Brief Bioinform., 2001, vol. 2, no. 3, pp. 245–257. https://doi.org/10.1093/bib/2.3.245

    Article  PubMed  CAS  Google Scholar 

  24. Ye, P. and Kirschner, D.E., Measuring emigration of human thymocytes by T-cell receptor excision circles, Crit. Rev. Immunol., 2002, vol. 22, nos. 5–6, pp. 483–497. PMID: 12803323.

    Article  PubMed  CAS  Google Scholar 

  25. Hazenberg, M.D., Otto, S.A., van Rossum, A.M., et al., Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1, Blood, 2004, vol. 104, no. 12, pp. 3513–3519. https://doi.org/10.1182/blood-2004-03-0805

    Article  PubMed  CAS  Google Scholar 

  26. De Boer, R.J. and Perelson, A.S., Quantifying T lymphocyte turnover, J. Theor. Biol., 2013, vol. 327, pp. 45–87. https://doi.org/10.1016/j.jtbi.2012.12.025

    Article  ADS  MathSciNet  PubMed  PubMed Central  CAS  Google Scholar 

  27. Gomolka, M., Oestreicher, U., Rößler, U., et al., Age-dependent differences in DNA damage after in vitro CT exposure, Int. J. Radiat. Biol., 2018, vol. 94, no. 3, pp. 272–281. https://doi.org/10.1080/09553002.2018.1419302

    Article  PubMed  CAS  Google Scholar 

  28. Ariyoshi, K., Miura, T., Kasai, K., et al., Age dependence of radiation-induced genomic instability in mouse hematopoietic stem cells, Radiat. Res., 2018, vol. 190, no. 6, pp. 623–633. https://doi.org/10.1667/RR15113.1

    Article  ADS  CAS  Google Scholar 

  29. Kovalchuk, I.P., Golubov, A., Koturbash, I.V., et al., Age-dependent changes in DNA repair in radiation-exposed mice, Radiat. Res., 2014, vol. 182, no. 6, pp. 683–694. https://doi.org/10.1667/RR13697.1

    Article  ADS  PubMed  CAS  Google Scholar 

  30. Vandevoorde, C., Vral, A., Vandekerckhove, B., et al., Radiation sensitivity of human CD34(+) cells versus peripheral blood T lymphocytes of newborns and adults: DNA repair and mutagenic effects, Radiat. Res., 2016, vol. 185, no. 6, pp. 580–590. https://doi.org/10.1667/RR14109.1

    Article  ADS  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors express their gratitude to V.A. Krivoshchapov and S.B. Epifanova for technical assistance in the work.

Funding

This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. I. Tolstykh.

Ethics declarations

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The authors used the results of cytogenetic studies obtained in 1994–2021 in the framework of several research projects. During each study period, the collection of biological samples was governed by applicable legislation, which was carefully followed. In each case, written informed consent was obtained from all donors for blood collection and participants involved in the study. To protect personal data, each donor was assigned a unique identification code, which was used in data analysis.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tolstykh, E.I., Vozilova, A.V., Degteva, M.O. et al. Dependence of the Translocation Frequency in Blood Lymphocytes on the Dose and Age at the Onset of Exposure in Residents of the Techa Riverside Settlements. Biol Bull Russ Acad Sci 50, 3184–3195 (2023). https://doi.org/10.1134/S106235902312021X

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S106235902312021X

Keywords:

Navigation