Department of Radiobiology

Research Topic

Our research focuses on effects of therapeutical and low doses of ionizing radiation, effects of microwaves/radiofrequency radiation and extremely low frequency (ELF) electromagnetic fields, human hematopoietic stem/progenitor cells, origination of and radiation risk factors for children leukemia, individual radiosensitivity of breast cancer patients. DNA damage response, gene and chromosome rearrangements, and apoptosis are the main endpoints studied by state-of-the art techniques including automated fluorescent and laser confocal microscopy, DNA repair foci and comet assays, FISH, RT-qPCR, DNA cloning and sequencing, standard and imaging flow cytometry, and cell sorting.

  • DNA damage response and preleukemic clones in hematopoietic stem cells in diagnostics, risk estimation and treatment of pediatric leukemia

A chromosomal translocation resulting in an in-frame preleukemic fusion gene (PFG) is often a primary genetic abnormality in the origination of acute childhood lymphoblastic/myeloid leukemia (ALL/AML). PFG arise in hematopoietic stem/progenitor cells (HSPC), often in utero. According to our results, about 1% of Slovak newborns harbor most frequent TEL-AML PGF in their umbilical cord blood (UCB). Our data have also suggested that only PGF arisen relatively early during embryonic/fetal development in specific HSPC population may facilitate overt leukemia in about 1% of PFG-positive newborns. Using a bank of UCB cells, we study FACS-sorted HSPC subpopulations from PGF positive UCB samples by RT-qPCR, DNA sequencing, and FISH. The obtained data may be used for early diagnostics of predisposition to ALL/AML and exclusion of UCB PGF positive samples from transplantation.

DNA damage response (DDR) and apoptosis are crucial for origination and persistence of PGF and may be impaired in HSPC of subjects predisposed to leukemia. Ionizing radiation at high doses is known to induce leukemia. Exposure to electromagnetic fields (EMF) has also been related to increased risk of childhood leukemia. However, no data are available whether ionizing radiation at low doses and EMF, to which significant part of general public is exposed in modern society, are able to induce PGF in HSPC and whether PGF may be used for assessment of risks for ALL/AML. Thus we study induction of PGF, DDR and apoptosis in HSPC subpopulations using state-of-the-art techniques.

Preleukemic HSPC are considered to be a cellular reservoir for relapses. We study diagnostically relevant PGF in HSPC subpopulations from PGF positive ALL/AML patients at diagnoses, remission, and relapse and in their backtracked UCB. The data will be correlated with clinical outcome to the aim of validation this approach for minimal residual disease (MRD), adjustment of treatment, and prevention of relapses.

  • Implementation of radiobiological research in radiotherapeutical practice

Proteins involved in formation of ionizing radiation induced foci (IRIF), such as tumor protein p53 (TP53) binding protein 1 (53BP1) and phosphorylated histone 2A family member X (gH2AX),  are considered to be the most sensitive molecular markers for DSB detection. We develop sophisticated experimental techniques to efficiently enumerate IRIF using imaging flow cytometry, laser confocal and fluorescent microscopy and validate their application for assessment of individual radiosensitivity of cancer patients and relative biological efficiency of proton therapy.

For the first time in Slovakia, we have introduced modern DNA repair techniques, which we have used to analyze the effects of gamma-rays and protons at therapeutic and low doses in human cells. We also founded the Radiobiology Laboratory at the Proton Therapeutic Center in Ruzomberok where we examined the relative biological activity of protons at therapeutic and low radiation doses. These data are useful for proton therapy planning. For the first time, we have developed effective methods of imaging flow cytometry to study endogenous DNA repair foci and also foci induced by low doses of radiation in human cells that could be used for various purposes including evaluation of individual radiosensitivity and epidemiological studies.

Predicting normal tissue radiosensitivity has yet to be routinely integrated into radiotherapy. The main objective of predictive testing is to tailor radiotherapy prescriptions to the individual patient in order to avoid side effects. The double strand breaks (DSB) repair and apoptosis is assumed to be a key factor in determination of individual side effects in response to radiation.  We analyze possibility to assess radiosensitivity of tumor cells based on endogenous and radiation-induced IRIF. This approach may provide efficient, reliable and fully atomized tool for estimation of tumor radiosensitivity prior radiotherapy.

Human hematopoietic stem cells (HSC) are thought to be a major target of radiation-induced leukemogenesis and also provide a relevant cellular model for assessing cancer risk. We analyze molecular markers of DNA repair and apoptosis in HSC with final aim to use them in molecular epidemiological studies of carcinogenicity.

  • Biological effects of non-ionizing electromagnetic radiation

While extremely low frequency (ELF) and radiofrequency (RF) electromagnetic fields (EMF) were classified by the International Agency on Research in Cancer ARC as carcinogen group 2B, the US Food and Drug Administration has approved healing of bone fractures by ELF at specific frequencies and RF EMF were used for treatment of different diseases including cancer in the ex-USSR countries. While the mechanisms remain elusive, most data indicate that of the EMF induce detrimental or beneficial effects in dependence on exposure conditions.  We focus on these mechanisms and molecular markers for analyzing EMF effects in therapeutical purpose and for assessment of cancer risk in in vitro and epidemiological studies.

 

Research Team

Doc. Ing. Igor Belyaev, DrSc.

Head of Department

+421 2 3229 5119


Igor Belyaev (101 publications, 1583 ISI citations, Hirsch index 23) received a diploma in physical engineering (Master of Science Degree) in Radiation Physics and Dosimetry from the Moscow Engineering Physics Institute (Moscow Technical University) in 1981; a Ph.D.  in Radiobiology from the Institute of Biophysics, USSR Academy of Science, Pushchino, USSR, in 1986; a Doctor of Science degree (a post Ph.D. degree, the highest post-graduate academic degree in the Soviet Union, Russia) in Genetics from St. Petersburg State University, St. Petersburg, Russia, in 1994; was named an Associate Professor of Toxicological Genetics by the Stockholm University, Stockholm, Sweden, in 2004. From 1981 to 1994, he held the positions of Research Scientist, Head of the Laboratory, and Head Research Scientist at the Department of Biophysics, Radiation Physics and Ecology at the Moscow Engineering Physics Institute.  From 1994 to 2006, he served as a visiting scientist, senior research scientist and group leader at Stockholm University in the Departments of Radiobiology, Molecular Genome Research, Genetic and Cellular Toxicology, Genetics, Toxicology and Microbiology. On-leave, 1994-2004, Moscow Engineering Physics, Institute, Igor Belyaev remains Leading Research Fellow on-leave from the Institute of General Physics, Russian Academy of Science, Moscow, Russia.

Igor Belyaev is now or formerly a member of: The Working Group of the International EMF Project of the World Health Organization, the Working group for the evaluation of RF carcinogenicity of the International Agency on Research in Cancer (IARC); the Stakeholder Dialogue Group on EMF, Health systems and Products, Risk Assessment, Health and Consumers of the Directorate-General, of the European Commission; the Memorial Fund Committee of the Bioelectromagnetics Society, the Swedish National Committee for Radioscience, the Russian National Committee on Non-Ionizing Radiation Protection, the EMF Working group of the European Academy for Environmental Medicine (EUROPAEM), the European Cancer and Environment Research Institute (ECERI),  and the European Association for Cancer Research. He serves as Associate Editor for the International Journal of Radiation Biology and on the Editorial Board of the Electromagnetic Biology and Medicine, Radiation Biology and Radioecology of the Russian Academy of Science. In 2011, he was awarded by the Bioelectromagnetics Society for the most influential paper in Bioelectromagnetics 2006-2010.

SCIENTIFIC STAFF

Eva Marková, RNDr. CSc., Deputy Head of Department

Milan Škorvaga, RNDr. CSc.

Pavol Košík, Mgr., PhD.

Matúš Durdík, Mgr., PhD.

Lukáš Jakl, Mgr., PhD.

SCIENTIFIC AND TECHNICAL STAFF

Lucián Zastko, Mgr.

Petra Petrovičová, Mgr.

PhD STUDENTS

Zlatka Černá, Mgr.

Mireia Vinas, Mgr.

  • Applications of Biological Dosimetry Methods in Radiation Oncology, Nuclear Medicine, Diagnostic and Interventional Radiology, International Atomic Energy Agency, IAEA RA No: 22259/R0, 14.07.2017-09.07.2021, zodpovedný riešiteľ Igor Belyaev, DrSc.
  • Biomarkery individuálnej citlivosti k žiareniu v terapii pacientok s nádorom prsníka, Vedecká grantová agentúra Ministerstva školstva, vedy, výskumu a športu Slovenskej republiky a Slovenskej akadémie vied (VEGA), 2/0147/17, 1.1.2017 / 31.12.2020, zodpovedný riešiteľ Marková Eva, PhD.
  • Odpoveď na poškodenie DNA a preleukemické klony v hematopoetických kmeňových bunkách v diagnostike, v stanovení rizika a v liečbe detskej leukémie, Agentúra na podporu výskumu a vývoja (APVV), APVV-15-0250, 1.7.2016 / 30.06.2019, zodpovedný riešiteľ Belyaev Igor, DrSc.
  • Mechanizmy účinkov nízkoúrovňového elektromagnetického žiarenia na priebeh onkologických ochorení, VEGA, 2/0089/18, 1.1.2018 / 30.06.2021, zodpovedný riešiteľ Belyaev Igor, DrSc.
  • Radiačne-indukované preleukemické génové fúzie v deliacich sa hematopoetických kmeňových/progenitorových bunkách pupočníkovej krvi, VEGA, 2/0087/18, 1.1.2018 / 30.06.2021, zodpovedný riešiteľ Škorvaga Milan, PhD.
  • Škorvaga M, Durdík M, Košík P, Marková E, Holop M, et al. (2018) Backtracked analysis of preleukemic fusion genes and DNA repair foci in umbilical cord blood of children with acute leukemia. Oncotarget 9: 19233-19244.
  • Misek J, Vojtek J, Veternik M, Kohan M, Jakusova V, et al. (2018) NEW RADIOFREQUENCY EXPOSURE SYSTEM WITH REAL TELECOMMUNICATION SIGNALS. Advances in Electrical and Electronic Engineering 16: 101-107.
  • Misek J, Belyaev I, Jakusova V, Tonhajzerova I, Barabas J, et al. (2018) Heart rate variability affected by radiofrequency electromagnetic field in adolescent students. Bioelectromagnetics 39: 277-288.
  • Makinistian L, Belyaev I (2018) Magnetic field inhomogeneities due to CO2 incubator shelves: a source of experimental confounding and variability? Royal Society open science 5: 172095.
  • Belyaev I (2018) Health effects of chronic exposure to radiation from mobile communication. In: Markov M, editor. Mobile Communications and Public Health. Boca Raton, London. New York: CRC Press. pp. 65-99.
  • Belpomme D, Hardell L, Belyaev I, Burgio E, Carpenter DO (2018) Thermal and non-thermal health effects of low intensity non-ionizing radiation: An international perspective. Environ Pollut 242: 643-658.
  • Kosik P, Skorvaga M, Durdik M, Jakl L, Nikitina E, et al. (2017) Low numbers of pre-leukemic fusion genes are frequently present in umbilical cord blood without affecting DNA damage response. Oncotarget 8: 35824-35834.
  • Durdik M, Kosik P, Kruzliakova J, Jakl L, Markova E, et al. (2017) Hematopoietic stem/progenitor cells are less prone to undergo apoptosis than lymphocytes despite similar DNA damage response. Oncotarget 8: 48846-48853.
  • Belyaev I (2017) Duration of Exposure and Dose in Assessing Nonthermal Biological Effects of Microwaves. In: Markov M, editor. Dosimetry in Bioelectromagnetics. Boca Raton, London. New York: CRC Press. pp. 171-184.
  • Portier CJ, Armstrong BK, Baguley BC, Baur X, Belyaev I, et al. (2016) Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA). J Epidemiol Community Health 70: 741-745.
  • Kosik P, Skorvaga M, Belyaev I (2016) Incidence of preleukemic fusion genes in healthy subjects. Neoplasma 63: 659-672.
  • Jakl L, Lobachevsky P, Vokalova L, Durdik M, Markova E, et al. (2016) Validation of JCountPro software for efficient assessment of ionizing radiation-induced foci in human lymphocytes. International Journal of Radiation Biology 92: 766-773.
  • Belyaev I, Dean A, Eger H, Hubmann G, Jandrisovits R, et al. (2016) EUROPAEM EMF Guideline 2016 for the prevention, diagnosis and treatment of EMF-related health problems and illnesses. Rev Environ Health 31: 363-397.
  • Markova E, Vasilyev S, Belyaev I (2015) 53BP1 foci as a marker of tumor cell radiosensitivity. Neoplasma 62: 770-776.
  • Markova E, Somsedikova A, Vasilyev S, Pobijakova M, Lackova A, et al. (2015) DNA repair foci and late apoptosis/necrosis in peripheral blood lymphocytes of breast cancer patients undergoing radiotherapy. International Journal of Radiation Biology 91: 934-945.
  • Kosik P, Skorvaga M, Durdik M, Jakl L, Markova E, et al. (2015) Low numbers of preleukemic gene fusion are frequently present in umbilical cord blood without affecting DNA damage response. European Journal of Cancer 51: S651-S651.
  • Jakl L, Lobachevsky P, Vokalova L, Markova E, Belyaev I (2015) Validation of new software for efficient assessment of radiation-induced DNA repair foci in human lymphocytes. European Journal of Cancer 51: S120-S121.
  • Durdik M, Skorvaga M, Kosik P, Markova E, Holop M, et al. (2015) Preleukemic gene fusions and DNA repair foci in umbilical cord blood from leukemia patients. European Journal of Cancer 51: S652-S652.
  • Durdik M, Kosik P, Gursky J, Vokalova L, Markova E, et al. (2015) Imaging flow cytometry as a sensitive tool to detect low-dose-induced DNA damage by analyzing 53BP1 and gammaH2AX foci in human lymphocytes. Cytometry A 4: 227-231.
  • Belyaev I, Somsedikova A, Markova E, Kubes M, Kolenova A, et al. (2015) Increased endogenous DNA damage in hematopoietic cells of ALL patients is associated with BCR-ABL and TEL-AML1 preleukemic gene fusions. European Journal of Cancer 51: S651-S651.
  • Belyaev I (2015) Biophysical Mechanisms for Nonthermal Microwave Effects. In: Markov M, editor. Electromagnetic Fields in Biology and Medicine. Boca Raton, London, New York: CRC Press. pp. 49-68.
  • Belyaev I (2015) Electromagnetic Field Effects On Cells And Cancer Risks From Mobile Communication. In: Rosch PJ, editor. Bioelectromagnetic and Subtle Energy Medicine. Boca Raton, London, New York: CRC Press. pp. 517-539.