Thesis
The role of nucleotides and the P2X7 receptor in radiation induced bystander effect
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2012
- Thesis identifier
- T13671
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- An interesting phenomenon, with possible implications for treatment related to radiotherapy is known as the bystander effect, whereby cells that have been irradiated initiate the destruction of neighbouring cells that have not been irradiated directly. The exact mechanisms that result in the bystander effect have yet to be fully identified. Purinergic signalling is a nucleotide based signalling pathway that involves both the P2Yand the P2X receptors and activation of these receptors regulate many different functions. The prolific and varied functions of purinergic signalling receptors and the processes they are involved with, either directly or indirectly, suggest a possible connection between purinergic signalling and the bystander effect. Aim: The aim of this project was to investigate the effect of changes in nucleotide availability on UVW/NAT cells and their ability to display the bystander effect following external beam radiation therapy. Additionally, the purinergic receptor P2X7 was targeted in order to study the effects of inhibiting this receptor on the bystander effect Method: The cell line UVW/NAT was used in these experiments. One group of cells were directly irradiated by external beam radiation and designated donor cells. The other group of cells were designated the recipient cells, as these cells received the transferred media from the irradiated donor cells but were never directly irradiated themselves. The reagents apyrase which breaks down ATP and ADP, ARL67156 which is a selective inhibitor of certain ectonucleotidases and A438079 which is a P2X7 receptor antagonist, were added to the donor cells to investigate their effect on the transmission of the bystander signal and to the recipient cells to investigate their effect on the receiving of the bystander signal. The effect was measured by determining the clonogenic survival of both the donor and recipient cells. Results: The reagent apyrase was added to both the donor and recipient cells and blocked the bystander effect. ARL67156 was added to the donor cells at a range of concentrations, at the lower concentration the bystander effect was not inhibited, at the highest concentration the bystander effect was blocked. When the high concentration was added to the recipient cells, the bystander effect was also blocked. A438079 was added to the donor cells and the bystander effect was blocked. When added to the recipient cells the bystander effect was blocked at 2 Gray (Gy) and 6Gy but at 1Gy had no effect, the bystander effect was not blocked at the low dose. Conclusion: Purinergic signalling is involved in both the transmission and reception of the bystander effect at some level. The exact nature of the connection remains unclear.
- Resource Type
- DOI
- Date Created
- 2012
- Former identifier
- 1005318
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