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Transcription Factors in the Cellular Response to Charged Particle Exposure

Hellweg, Christine E. and Spitta, Luis F. and Henschenmacher, Bernd and Diegeler, Sebastian and Baumstark-Khan, Christa (2016) Transcription Factors in the Cellular Response to Charged Particle Exposure. Frontiers in Oncology, 6. Frontiers Media S.A.. DOI: 10.3389/fonc.2016.00061 ISSN 2234-943X

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Official URL: http://dx.doi.org/10.3389/fonc.2016.00061

Abstract

Charged particles, such as carbon ions, bear the promise of a more effective cancer therapy. In human spaceflight, exposure to charged particles represents an important risk factor for chronic and late effects such as cancer. Biological effects elicited by charged particle exposure depend on their characteristics, e.g., on linear energy transfer (LET). For diverse outcomes (cell death, mutation, transformation, and cell-cycle arrest), an LET dependency of the effect size was observed. These outcomes result from activation of a complex network of signaling pathways in the DNA damage response, which result in cell-protective (DNA repair and cell-cycle arrest) or cell-destructive (cell death) reactions. Triggering of these pathways converges among others in the activation of transcription factors, such as p53, nuclear factor κB (NF-κB), activated protein 1 (AP-1), nuclear erythroid-derived 2-related factor 2 (Nrf2), and cAMP responsive element binding protein (CREB). Depending on dose, radiation quality, and tissue, p53 induces apoptosis or cell-cycle arrest. In low LET radiation therapy, p53 mutations are often associated with therapy resistance, while the outcome of carbon ion therapy seems to be independent of the tumor’s p53 status. NF-κB is a central transcription factor in the immune system and exhibits pro-survival effects. Both p53 and NF-κB are activated after ionizing radiation exposure in an ataxia telangiectasia mutated (ATM)-dependent manner. The NF-κB activation was shown to strongly depend on charged particles’ LET, with a maximal activation in the LET range of 90–300 keV/μm. AP-1 controls proliferation, senescence, differentiation, and apoptosis. Nrf2 can induce cellular antioxidant defense systems, CREB might also be involved in survival responses. The extent of activation of these transcription factors by charged particles and their interaction in the cellular radiation response greatly influences the destiny of the irradiated and also neighboring cells in the bystander effect.

Item URL in elib:https://elib.dlr.de/103577/
Document Type:Article
Title:Transcription Factors in the Cellular Response to Charged Particle Exposure
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Hellweg, Christine E.Cellular Biodiagnostics, Department of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Cologne, Germany; christine.hellweg (at) dlr.deUNSPECIFIED
Spitta, Luis F.Cellular Biodiagnostics, Department of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Cologne, GermanyUNSPECIFIED
Henschenmacher, BerndCellular Biodiagnostics, Department of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Cologne, GermanyUNSPECIFIED
Diegeler, SebastianCellular Biodiagnostics, Department of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Cologne, GermanyUNSPECIFIED
Baumstark-Khan, ChristaCellular Biodiagnostics, Department of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Cologne, GermanyUNSPECIFIED
Date:2016
Journal or Publication Title:Frontiers in Oncology
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:6
DOI :10.3389/fonc.2016.00061
Publisher:Frontiers Media S.A.
ISSN:2234-943X
Status:Published
Keywords:charged particles, p53, Nrf2, NF-κB, AP-1, Sp1, CREB, EGR-1
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Strahlenbiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Deposited By: Kopp, Kerstin
Deposited On:23 Mar 2016 10:50
Last Modified:08 Mar 2018 18:38

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