Division of Cellular and Immune-radiobiology
A. Research activity
The main research activity of the Division of Cellular and Immune Radiobiology represents the study of cellular and molecular effects of ionizing radiation.
The biological effects of low-dose (below 100 mGy) ionizing radiation.
The importance of the topic: The number of diagnostic medical examinations (CT, PET, PET-CT, and angiography) which imply low-dose radiation exposure, increased rapidly during the last decade and this is also a future tendency. These procedures affect the population on a wide scale. The doses received during a single intervention are very low, and they will not result in short term health impairment. Low dose induced long term effects are less well identified One of the main research activity of the division is to study short and long term biological effects of low dose ionizing radiation in various biological systems.
Low dose research constitutes the main research priority of the EU EURATOM organization. The financial support of the division for its low dose research activity is assured by various EU funded international collaborative projects. The division was a member of the FP6 NOTE project, which ended in 2010. Our main research task was to study low dose ionizing radiation effects on the immune system.
Another topic constitutes the study of low dose effects on long-term brain damage in murine and rat models. We investigate low dose irradiation induced damage in blood-brain barrier permeability, radiation induced inflammatory processes affecting the brain microcirculation in general and microvascular endothelial cells in special, and radiation induced mitochondrial dysfunction. This topic, which is carried out between 2011 and 2014, is financed by the EU FP-7 CEREBRAD project(http://www.cerebrad-fp7.eu/).
In 2013, as a result of an external call aiming at recruiting new partners we became members of the DoReMi Network of Excellence (http://www.doremi-noe.net/index.html). Our main task in this consortium is to investigate low dose irradiation induced fenotypical and functional alteration in brain pericytes in murine models.
Other research topics: Combined treatment of experimental tumors with gene- and radiotherapy
The aim is to enhance the radiosensitivity of tumors by the means of gene therapy. Certain chemotherapeutic drugs were shown to improve the efficiency of radiotherapy, they behave as radiosensitizers. Such a drug is gemcitabine, which is a nucleoside analog. The drug itself is inactive, it becomes active during its intracellular metabolism. This metabolic activation is mainly done by the deoxycytidine kinase, but other enzymes are also involved. Our aim is to enhance the cytotoxic and radiosensitizing effect of gemcitabine by modulating the activity of the enzymes involved in the metabolization of this drug, and by using gene therapy.
B. Teaching activity
We keep lectures at several universities on the following training courses:
- Comprehensive and modern radiation protection course organized by Semmelweis University, Budapest and NRRI
- Radiation biology course for radiotherapy specialists and candidates at Semmelweis University, Budapest
- Radiation biology course for undergraduate students at University of Pécs
- Postgradual radiation biology for radiation physicists at Budapest University of Technology and Economics
We participate in the practical training of radiation biology for radiotherapy specialist candidates.
C. Relevant publications:
- Lumniczky K, Sáfrány G. Simultaneous isolation of both RNA and DNA from many small tissue samples. Acta Biologica Hungarica, 1997; 48: 253-257.
- Lumniczky K, Antal S, Unger E, Hídvégi EJ, Sáfrány G. Oncogenic changes in murine lymphoid tumors induced by in utero exposure to ionizing radiation. Radiat. Oncol. Invest. 1997; 5: 158-162.
- Lumniczky K, Antal S, Unger E, Wunderlich L, Hídvégi EJ and Sáfrány G. Carcinogenic alterations in murine liver, lung and uterus tumors induced by in utero exposure to ionizing radiation. Mol. Carcinogen. 1998; 21: 100-110
- Schmidt J, Lumniczky K, Tzschaschel BD, Guenther HL, Luz A, Riemann S, Gimbel W, Erfle V, Erben RG. Onset and dynamics of osteosclerosis in mice induced by RFB murine leukemia virus (RFB MuLV): Increase in bone mass precedes lymphomagenesis. The American Journal of Pathology 1999; 155: 557-570
- Désaknai S, Lumniczky K, Hidvégi EJ, Hamada H, Sáfrány G. Brain tumor treatment with IL-2 and IL-12 producing autologous cancer cell vaccines. Adv. Exp. Med. Biol. 2001; 495: 369-372.
- Lumniczky K, Désaknai S, Mangel L, Szende B, Hamada H, Hidvégi EJ, Sáfrány G. Local tumor irradiation augments the anti-tumor effect of cytokine producing autologous cancer cell vaccines in a murine glioma model. Cancer Gene Ther. 2002; 9: 44-52.
- Antal S, Lumniczky K, Palfalvi J, Hidvegi E, Schneider F, Safrany G. Oncogenes and tumor suppressor genes in murine tumors induced by neutron- or gamma-irradiation in utero. RADIATION AND HOMEOSTASIS, INTERNATIONAL CONGRESS SERIES. 1236: 119-122. 2002
- Désaknai S, Lumniczky K, Ésik O, Hamada H, Sáfrány G. Local tumour irradiation enhances the anti-tumour effect of a double-suicide gene therapy system in a murine glioma model. J Gene Med 2003; 5: 377-385.
- Klementis I, Lumniczky K, Kis E, Szatmári T, Antal S, Sáfrány G. The transgenerational mutagenic and carcinogenic effect of ionizing radiation. Central European Journal of Occupational and Environmental Medicine 2004; 10: 235-245.
- K. Lumniczky and G. Sáfrány. The bystander effect of cancer gene therapy. In „Non-targeted effects of ionising radiation Proceedings of the RISC-RAD specialised training course. STUK – Radiation and Nuclear Safety Authority, Helsinki, Finland 14 – 16 February 2005 (Ed. O. Belyakov)
- Szatmári T*, Lumniczky K*(shared first-authorship), Désaknai S, Trajcevski S, Hídvégi EJ, Hamada H, Sáfrány G. Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Science 2006; 97: 546-553.
- Lumniczky K, Sáfrány G. Cancer Gene Therapy: Combination with Radiation Therapy and the Role of Bystander Cell Killing in the Anti-tumor Effect. Pathol Oncol Res 2006; 12:118-24.
- Kis E, Szatmári T, Keszei M, Farkas R, Ésik O, Lumniczky K, Falus A, Sáfrány G. Microarray analysis of radiation response genes in primary human fibroblasts. Int J Radiat Oncol Biol Phys 2006; 66:1506-14.
- Szatmári T, Huszty G, Désaknai S, Spasokoukotskaja T, Sasvári-Székely M, Staub M, Ésik O, Sáfrány G, Lumniczky K. Adenoviral vector transduction of the human deoxycytidine kinase gene enhances the cytotoxic and radiosensitizing effect of gemcitabine on experimental gliomas. Cancer Gene Ther 2008; 15: 154-64.
- Bogdándi EN, Balogh A, Felgyinszky N, Szatmári T, Persa E, Hildebrandt G, Sáfrány G, Lumniczky K. Low Dose Radiation Effects on the Immune System of Mice after Total-body Irradiation. Radiat Res 2010, 174: 480-489.
- Hargita Hegyesi, Nikolett Sándor, Boglárka Schilling, Enikő Kis, Katalin Lumniczky, Géza Sáfrány. Differentially expressed genes associated with low-dose gamma radiation: Growth Differentiation Factor (GDF-15) as a radiation response gene and radiosensitizing target. Springer Radiation Damage in Biomolecular Systems Biological and Medical Physics, Biomedical Engineering, EDsGarcia and M.C. Fuss: 2012, Part 3, 359-370
- Balogh A, Persa E, Bogdándi EN, Benedek A, Hegyesi H, Sáfrány G, Lumniczky K. The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells. Inflamm Res 2013, 62: 201-212. DOI 10.1007/s00011-012-0567-y
- Mothersill C, Antonelli F, Dahle J, Dini V, Hegyesi H, Iliakis G, Kämäräinen K, Launonen V, Lumniczky K, Lyng F, Safrany G, Salomaa S, Schilling-Tóth B, Tabocchini A, Kadhim MA. A laboratory inter-comparison of the importance of serum serotonin levels in the measurement of a range of radiation-induced bystander effects: overview of study and results presentation. Int J Radiat Biol 2012, 88; 763.
- Lumniczky K, Sáfrány G. The Impact of Radiation Therapy on the Antitumor Immunity: Local Effects and Systemic Consequences. Cancer Letters 2013 http://dx.doi.org/10.1016/j.canlet.2013.08.024