Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines

Abstract

Purpose: To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure.

Materials and methods: Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells.

Results: We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy.

Conclusion: These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.

Keywords:

• Bystander effect
• calcium flux
• esophageal adenocarcinoma
• hyper-radiosensitivity
• p53

Acknowledgements

This work was funded by the Natural Sciences and Engineering Research Council of Canada (RGPIN293153-12). We acknowledge Dr Niamh Lynam-lennon from Trinity College Dublin, Ireland for the OE33 cell lines. We also acknowledge Dr Cristian Fernandez for performing the LQ and IR model fits for the cell survival curves.

Disclosure statement

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