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DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals

Oncogene volume 27, pages 6761–6769 (2008)Cite this article

Abstract

The phenomenon by which irradiated cells influence non-irradiated neighboring cells, referred to as the bystander effect (BSE), is not well understood in terms of the underlying pathways involved. We sought to enlighten connections between DNA damage repair and the BSE. Utilizing sister chromatid exchange (SCE) frequencies as a marker of the BSE, we performed cell transfer strategies that enabled us to distinguish between generation versus reception of a bystander signal. We find that DNA-dependent Protein Kinase catalytic subunit (DNA-PKcs) and Ataxia Telangectasia Mutated (ATM) are necessary for the generation of such a bystander signal in normal human cells following gamma (γ)-ray exposure, but are not required for its reception. Importantly, we also show that directly irradiated human cells do not respond to receipt of a bystander signal, helping to explain why the BSE is a low-dose phenomenon. These studies provide the first evidence for a role of the DNA damage response proteins DNA-PKcs and ATM specifically in the generation of a bystander signal and intercellular signaling.

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Acknowledgements

We thank Dakim Gaines for technical assistance. Support for this research is gratefully acknowledged from the NIH/NCI, Grants CA-09236-30 (RLU) and CA-043322-20 (RLU and SMB), the US Department of Energy (DOE), Grant DE-FG02-01ER63239 (RLU and SMB), and from the National Aeronautics and Space Administration (NASA), Grant NNJ04HD83G (SMB).

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Author notes

  1. R T Hagelstrom, K F Askin and A J Williams: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA

    R T Hagelstrom, K F Askin, A J Williams, L Ramaiah, R L Ullrich & S M Bailey

  2. Laboratory of Radiobiology, SCK·CEN (Studiecentrum voor kernenergie-Centre d'étude de l'énergie nucléaire), Boeretang 200, MOL, Belgium

    C Desaintes

  3. KromaTiD Inc., Fort Collins, CO, USA

    E H Goodwin

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  1. R T Hagelstrom
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  2. K F Askin
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Correspondence to S M Bailey.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Hagelstrom, R., Askin, K., Williams, A. et al. DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. Oncogene 27, 6761–6769 (2008). https://doi.org/10.1038/onc.2008.276

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