englishslovensky
Laboratory of Radiobiology
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. 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. 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 PCR, 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.
Head of laboratory: Beliaev Igor

Scientists
  • Beliaev Igor
  • Košík Pavol
  • Marková Eva
  • Škorvaga Milan
PhD students
  • Durdík Matúš
  • Jakl Lukáš
  • Somsedíková Alexandra
Others
  • Petrovičová Petra
  • Zastko Lucián
  • Šumichrastová Anna
Projects

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