Abstract
Purpose: Widespread medical use of radiation in diagnosis, imaging and treatment of different central nervous system malignancies lead to various consequences. Aim of this study was to further elucidate mechanism of cell response to radiation and possible consequence on neural differentiation.
Materials and methods: NT2/D1 cells that resemble neural progenitors were used as a model system. Undifferentiated NT2/D1 cells and NT2/D1 cells in the early phase of neural differentiation were irradiated with low (0.2 Gy) and moderate (2 Gy) doses of γ radiation. The effect was analyzed on apoptosis, cell cycle, senescence, spheroid formation and the expression of genes and miRNAs involved in the regulation of pluripotency or neural differentiation.
Results: Two grays of irradiation induced apoptosis, senescence and cell cycle arrest of NT2/D1 cells, accompanied with altered expression of several genes (SOX2, OCT4, SOX3, PAX6) and miRNAs (miR-219, miR-21, miR124-a). Presented results show that 2 Gy of radiation significantly affected early phase of neural differentiation in vitro.
Conclusions: These results suggest that 2 Gy of radiation significantly affected early phase of neural differentiation and affect the population of neural progenitors. These findings might help in better understanding of side effects of radiotherapy in treatments of central nervous system malignancies.
Disclosure statement
The authors report no conflicts of interest.
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Notes on contributors
Danijela Stanisavljevic
Dr. Danijela Stanisavljevic is a Research Associate in Human Molecular Genetics Laboratory, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade. Her research interest: molecular mechanisms involved in neural development and malignant transformation of cell.
Jelena Popovic
Dr. Jelena Popovic is a Senior Research Associate in Human Molecular Genetics Laboratory, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade and a member of the Scientific Council of the same Institution. Her research interests: molecular pathways involved in cancer development/progression and improving efficiency in radiation therapy.
Isidora Petrovic
Dr. Isidora Petrovic is a Research Associate in Human Molecular Genetics Laboratory, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade. Her research interest: human molecular genetics, cancer biology, screening for novel bioactive and synthetic drugs.
Slobodan Davidovic
Dr. Slobodan Davidovic is a Research Associate in Human Molecular Genetics Laboratory, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade. His research interests: analysis of molecular diversity of Serbian population based on mitochondrial DNA polymorphisms and analysis of cytotoxic and anti-cancerogenic potential of bioactive compounds isolated from fungus/plants.
Michael J. Atkinson
Prof. Dr. Michael J. Atkinson is a full Professor at Medical Faculty, Technical University Munich (TUM) and Director of the Institute of Radiation Biology at Helmholtz Zentrum München, with research interest: radiation biology, radiation protection, molecular genetics.
Nataša Anastasov
Dr. Nataša Anastasov is a principal investigator at Institute of Radiation Biology, Helmholtz Zentrum München and lecturer at Medical Faculty, Technical University Munich (TUM) for program Master in Radiation Biology. Her research interest: radiation biology and oncology, drug screening, lentiviral gene therapy tools.
Milena Stevanovic
Academician Milena Stevanovic is full member of Serbian Academy of Sciences and Arts, full Professor at Faculty of Biology, University of Belgrade, Head of Human Molecular Genetics Laboratory, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade. Research interest: human molecular genetics, maintaining pluripotency and neural differentiation of stem cells; cytotoxic, antioxidant and anticancer properties of natural and synthetic compounds, molecular phylogenetic.