Use this URL to cite or link to this record in EThOS:
Title: Investigation of cellular responses to modulated radiation fields in transitional cell carcinoma and normal bladder urothelium : a role for radiation inducted bystander signalling
Author: Bill, Malgorzata Anna
ISNI:       0000 0004 5369 1140
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2014
Availability of Full Text:
Access from EThOS:
Bladder cancer is the second most common genitourinary malignancy. Radiotherapy is a treatment of choice for patients. As new modern radiation treatments such as intensity-modulated radiation therapy are being introduced, there is the need to analyse responses and underlying mechanisms to modulated field exposures. The aim of the current project was to investigate the responses to uniform and modulated radiation fields of two bladder cancer cell lines T24 and HT1376 and normal urothelial cells. Mechanisms underpinning bystander responses and the role of ATP and Ca2+ signalling was analysed. Experiments showed that the HT1376 cell line was the most radioresistant and normal urothelial cells the most radiosensitive of the three cell lines tested. Subsequent analysis showed a correlation between radiosensitivity and response to modulated field exposures. clonogenic cell survival radiation induced foci. The role of ATP as a bystander signalling to modulated field exposure was also demonstrated. A radiation induced increase in extracellular ATP occurred in T24 but not HT1376 or normal urothelial cells. Data shows ATP to evoke ci+ transients, indicating its co-regulation. Measurements indicated higher baseline ATP extracellular levels in the bladder cancer cell lines than in normal urothelial cells. This correlated with the differences in spontaneous activity patterns, where normal cells did not show spontaneous Ca2+ transients while the two bladder cancer cell lines did. Further analysis with apyrase (ectonucleotidase) and ARL67156 ectonucleotidase inhibitor indicated differences in purinergic signalling prpertiesof normal and cancer cells linked to a role for ATP in spontaneous Ca2 + activity in bladder cancer cell lines. Treatment of T24, HT1376 and normal urothelial cells with ATP reduced clonogenic cell survival indicating that ATP can affect cell proliferation. Interestingly apyrase, ARL67156 as well as P2 receptor blockers treatment caused a decrease in clonogenic cell survival of T24 cells showing that purinergic mechanisms regulating proliferation are complex.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available