A role for p53 in the response of bystander cells to receipt of medium borne signals from irradiated cells

Abstract

Purpose: A number of contradictory studies have reported a role or not for p53 (protein 53) in the production of radiation-induced bystander effects. Most of these studies looked at a range of cell lines with normal or compromised p53 function.

Methods: In this study, Human Colon Tumour line 116 (HCT 116) cells with confirmed wild type p53 function and a corresponding p53 null HCT 116 line were used to test for bystander signal production and response to bystander signals in a mix/match protocol using the medium transfer technique.

Results: The results showed that both the null cells and the wild type cells produced bystander signals. However, only the p53 wild type cells responded to signals from either cell line. The Human Papilloma Virus transfected keratinocyte line G (HPV-G) reporter cell line used routinely in our laboratory was used to confirm that the null cells were producing signals.

Conclusions: We conclude that in this system the p53 pathway is involved in response of cells to bystander signals but that signals can be produced by cells which do not have functional p53. If these results apply in vivo, they could be important in radiotherapy where tumours may have compromised p53 function but surrounding (and distant) normal tissue may have wild type functional p53.

Keywords::

• Bystander effects
• p53
• non-targeted effects of radiation
• low dose effects of radiation

Acknowledgements

We acknowledge the continued support of the Canada Research Chairs and the Natural Science and Engineering Research Council (NSERC) Industrial Research Chairs Programmes. We also acknowledge our partners in the European Union's Non-Targeted Effects (NOTE) integrated project.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.