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Abstract
Purpose: The recent rapid increase of hadron therapy applications requires the development of high performance, reliable in vivo models for preclinical research on the biological effects of high linear energy transfer (LET) particle radiation.
Aim: The aim of this paper was to test the relative biological effectiveness (RBE) of the zebrafish embryo system at two neutron facilities.
Material and Methods: Series of viable zebrafish embryos at 24-hour post-fertilization (hpf) were exposed to single fraction, whole-body, photon and neutron (reactor fission neutrons (<En = 1 MeV>) and (p (18 MeV)+Be, <En> = 3.5 MeV) fast neutron) irradiation. The survival and morphologic abnormalities of each embryo were assessed at 24-hour intervals from the point of fertilization up to 192 hpf and then compared to conventional 6 MV photon beam irradiation results.
Results: The higher energy of the fast neutron beams represents lower RBE (ref. source LINAC 6 MV photon). The lethality rate in the zebrafish embryo model was 10 times higher for 1 MeV fission neutrons and 2.5 times greater for p (18 MeV)+Be cyclotron generated fast neutron beam when compared to photon irradiation results. Dose-dependent organ perturbations (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, pericardial edema and inhibition of yolk sac resorption) and microscopic (marked cellular changes in eyes, brain, liver, muscle and the gastrointestinal system) changes scale together with the dose response.
Conclusion: The zebrafish embryo system is a powerful and versatile model for assessing the effect of ionizing radiation with different LET values on viability, organ and tissue development.
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
Notes on contributors
E. R. Szabó
Emília Rita Szabó is a last-year PhD student at the ELI-HU Nonprofit Ltd. in collaboration with the University of Szeged. She received a master’s degree in biology from the University of Cluj-Napoca, Romania. Her current research field is the establishment of the zebrafish embryo model to study the effects of different radiation qualities and definition of the RBE.
Z. Reisz
Zita Reisz is a resident pathologist at the Department of Pathology, University of Szeged. She received her master’s degree in medicine from the University of Szeged. She is involved in university education and her speciality is neuropathology as well as his research field is the histological diagnosis of CNS tumors.
R. Polanek
Róbert Polanek is a first-year PhD student at the ELI-HU Nonprofit Ltd. in collaboration with the University of Szeged. He received a master’s degree in physics from the University of Cluj-Napoca, Romania. His current research field is the establishment of different dosimetry systems.
T. Tőkés
Tünde Tőkés is a postdoctoral researcher at the ELI-HU Nonprofit Ltd. She received a master’s degree in biology and got her PhD degree in Graduate School of Multidisciplinar Medical Sciences from the University of Szeged, Hungary. Her research topic is the investigation of the acute and late consequences of irradiation.
Sz. Czifrus
Szabolcs Czifrus is an associate professor and director of Institute of Nuclear Techniques at Budapest University of Technology and Economics. He received a master’s degree in physics from the Eötvös Loránd University of Sciences. His research area is IV. reactor physics of generation reactors, Monte Carlo particle transport methods, nuclear fuel cycle.
Cs. Pesznyák
Csilla Pesznyák is an associate professor at the Institute of Nuclear Techniques at Budapest University of Technology and Economics. She received her master’s degree in physics from the Faculty of Natural Sciences and Mathematics of the University of Novi Sad, and got her biomedical engineer PhD degree from Semmelweis University, Budapest. Her field of research is radiotherapy, including teletherapy irradiation techniques, dosimetry, quality assurance, radiation biology, radiation protection and education organization.
B. Biró
Barna Biró is a junior research fellow at the Hungarian Academy of Sciences Institute for Nuclear Research (MTA Atomki), Debrecen, Hungary. He received a master’s degree in physics from the University of Cluj-Napoca, Romania. His current research field is the exploration and development of a novel control software framework for research infrastructures.
A. Fenyvesi
András Fenyvesi is a senior research associate, head of organizational unit at the laboratory of cyclotron applications. His current research topic is neutron physics, industrial and medical applications. Projects in which he participates: National Nuclear Research Program of Hungary, Complex Innovation - health industry network for efficiency improvement, exploration and development of a novel control software framework for research infrastructures, CMS experiment of the Large Hadron Collider in Hungary.
B. Király
Beata Király is a research associate at the Hungarian Academy of Sciences Institute for Nuclear Research (MTA Atomki), Debrecen, Hungary. Her field of research is the Central Nervous System Imaging, health industry network for efficiency improvement and exploration as well as development of a novel control software framework for research infrastructures.
J. Molnár
József Molnár is a senior research associate and technical director at the Hungarian Academy of Sciences Institute for Nuclear Research (MTA Atomki), Debrecen, Hungary. His current research field is the experimental particle physics, measurement of radiation tolerance, detector developments, study of infrared in the vicinity of interferometric gravity wave detectors and surveying chemical processes on the surface with positron emissive tomography.
Sz. Brunner
Szilvia Brunner is a first-year PhD student at the ELI-HU Nonprofit Ltd. in collaboration with the University of Szeged. She received a master’s degree in biology from the University of Szeged, Hungary. Her current research field is the examination of the acute effects of irradiation.
B. Daroczi
Borbála Daroczi is a research associate, at the Department of Internal Medicine, Division of Geriatrics, University of Debrecen, Hungary. She received her master’s degree in medicine from the University of Debrecen, and got her PhD degree in Doctoral School of Clinical Medicine from the University of Szeged. Her current research field is the evaluation of agents that can modify the radiation response.
Z. Varga
Zoltán Varga is a scientific associate, physicist at the Department of Oncotherapy, University of Szeged. He received a master’s degree in physics, and PhD degree from the University of Szeged. His current research field is radiation therapy, dosimetry.
K. Hideghéty
Katalin Hideghéty is associate professor at the Department of Oncotherapy, University of Szeged and a group leader at the ELI-HU Nonprofit Ltd. in Hungary. She received her master’s degree in medicine from the University of Szeged, and got her PhD degree from University of Pécs and her habilitation was performed at University Szeged. Her research field is the optimization of radiotherapy for brain, skin, head and neck and gastrointestinal tumors both in clinical studies and in preclinical investigations, with special focus on novel techniques such as laser driven ionizing radiation, BNCT, microbeam RT, and hadron therapy.