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Improved cellular survival of bystander cells via NF-κB associated recovery after X-irradiation

Diegeler, Sebastian and Baumstark-Khan, Christa and Hellweg, Christine Elisabeth (2017) Improved cellular survival of bystander cells via NF-κB associated recovery after X-irradiation. 4th German-French DNA Repair Meeting, 21.-23. September 2017, Cologne, Germany.

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Radiation-induced bystander effects (RIBE) are an acknowledged issue of radiation therapy. Radiation of tumor tissue has been shown to affect non-irradiated neighboring cells in a paracrine and endocrine manner. Transduction of bystander signaling though remains to be investigated in detail. A part of the transduction is the receptor-initiated activation of signaling pathways by secreted factors of the irradiated cell during irradiation damage response. This work focusses on the activation of the transcription factor Nuclear Factor kappaB (NF-kappaB) in bystander cells after irradiation. NF-kappaB is a well-known contributor to inflammatory processes like cyto- / chemokine production as well as to stress reactions such as the DNA damage response and cell cycle regulation. Using a mouse embryonic fibroblasts (MEF) in vitro model with a genetic knock-out of an NF-kappaB regulator (NEMO, NF-kappaB essential modulator), clonogenic survival and cell cycle distribution was determined in directly irradiated cells and in cells incubated with conditioned medium from X-irradiated cells (bystander treatment). Directly irradiated NEMO ko cells, plated for clonogenic survival immediately after X-irradiation, display the same dose-effect curve as the wildtype (wt) (a/b NEMO ko = 13.92 ± 2.4 vs. a/b wt = 12.37 ± 2.6). But when allowed to recover for 24 h, the wt cells show a broader shoulder in the curve (a/b = 3.5 ± 2.9), indicating a role of NF-kappaB in the repair of radiation induced DNA damages. Looking into the survival of bystander cells, the survival curves show a statistically different slope, with NEMO ko cells surviving better than wt cells (S16 Gy: NEMO ko = 1.66 vs wt = 0.83). The different behavior may correlate with NF-kappaB dependent DNA repair in bystander cells for NEMO ko and wt cells. Cell cycle analysis revealed a 6 hour delayed arrest in G2/M phase in directly irradiated NEMO ko cells compared to wt cells. This indicates that NF-kappaB regulated DNA repair pathways are important for recovery of radiation induced damages. Bystander NEMO ko show an even further delayed arrest at 48 h, while wt bystander cells show no G2/M arrest at all. This supports the assumption that damages have to overcome a certain threshold to be recognized as repair-worthy. As NF-kappaB has been reported to be involved in homologous recombination; cells with impairment in NF-kappaB pathways, such as NEMO ko, register damages caused by bystander treatment differently from wt cells. This leads to G2/M arrest extending time for repair in NEMO ko bystander cells.

Item URL in elib:https://elib.dlr.de/118029/
Document Type:Conference or Workshop Item (Poster)
Title:Improved cellular survival of bystander cells via NF-κB associated recovery after X-irradiation
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Baumstark-Khan, Christaradiation biology department, institute of aerospace medicine, german aerospace center (dlr), cologne, germanyUNSPECIFIED
Hellweg, Christine ElisabethUNSPECIFIEDhttps://orcid.org/0000-0002-2223-3580
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In ISI Web of Science:No
Keywords:Radiation-induced bystander effects (RIBE), Nuclear Factor kappaB (NF-kappaB), X-irradiation
Event Title:4th German-French DNA Repair Meeting
Event Location:Cologne, Germany
Event Type:international Conference
Event Dates:21.-23. September 2017
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 - Research under Space Conditions
DLR - Research theme (Project):R - Vorhaben Strahlenbiologie (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Deposited By: Kopp, Kerstin
Deposited On:11 Jan 2018 13:41
Last Modified:31 Jul 2019 20:15

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