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Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

Growth Differentiation Factor (GDF-15) as a radiation response gene and radiosensitizing target

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Radiation Damage in Biomolecular Systems

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent’s whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300–500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

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Acknowledgments

This work was supported by the following grants: the European Union NOTE project (FP6-036465/2006), Hungarian OTKA K77766 and ETT 827-1/2009. The authors thank the expert technical assistance of Ms. Mária Frigyesi and Ms. Rita Lőkös.

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Authors and Affiliations

  1. Department of Molecular and Tumor Radiobiology, F. Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Anna 5, Budapest, 1221, Hungary

    Hargita Hegyesi, Nikolett Sándor, Boglárka Schilling, Enikő Kis, Katalin Lumniczky & Géza Sáfrány

Authors
  1. Hargita Hegyesi
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  2. Nikolett Sándor
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  3. Boglárka Schilling
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  4. Enikő Kis
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  6. Géza Sáfrány
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Correspondence to Hargita Hegyesi .

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  1. , Consejo Superior de Investigaciones Cien, Instituto de Física Fundamental (IFF), Serrano 113-bis, Madrid, 28006, Spain

    Gustavo García Gómez-Tejedor

  2. Consejo Superior de Investigaciones Cien, Instituto de Física Fundamental (IFF), Serrano 113bis, Madrid, 28006, Spain

    Martina Christina Fuss

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Hegyesi, H., Sándor, N., Schilling, B., Kis, E., Lumniczky, K., Sáfrány, G. (2012). Differentially Expressed Genes Associated with Low-Dose Gamma Radiation. In: García Gómez-Tejedor, G., Fuss, M. (eds) Radiation Damage in Biomolecular Systems. Biological and Medical Physics, Biomedical Engineering. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2564-5_21

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  • DOI: https://doi.org/10.1007/978-94-007-2564-5_21

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  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-2563-8

  • Online ISBN: 978-94-007-2564-5

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