Document Type

Theses, Ph.D

Rights

This item is available under a Creative Commons License for non-commercial use only

Disciplines

1.6 BIOLOGICAL SCIENCES

Publication Details

Successfully submitted for the award of Doctor of Philosophy (Ph.D) to the Dublin Institute of Technology, 2014.

Abstract

The overall aim of this study was to investigate the cellular and molecular mechanisms involved in radiation-induced bystander effects in HaCaT cells, predominantly at low-doses of irradiation. They do not follow the original dose-response theory and exhibit a unique cascade of signalling events, which are under intense investigation for radiation risk purposes. An in vitro system was first used to observe the bystander effect, comparing two cell viability assays while measuring apoptotic cell death in these known reporter HaCaT cells and established the most sensitive assay for bystander responses Downstream bystander signalling events were then investigated through gene expression studies of apoptotic genes over a complex time-course with different low doses to reveal very specific changes in bystander responses. The expression pattern profile revealed novel unique bystander-induced apoptotic signalling pathways in different low doses of irradiation. Proteomic methods using 2D gel electrophoresis and mass spectroscopy further revealed novel proteins which were significantly over or under–expressed in the bystander reporter cells but using an ex-vivo fish model. These results revealed an induction of protection of the cells in response to oxidative stress and modulation of cell death processes. The data generated in this thesis has led to the proposal of two distinct and comparative signalling pathways of a cellular radiation induced bystander response for 0.05 Gy and 0.5 Gy ionising radiation. These novel pathways have expanded our knowledge in the cellular and molecular mechanisms which occur when a cell receives a bystander signal and may have future clinical considerations and implications for patients undergoing radiotherapy treatment plans.

DOI

10.21427/D7XW29

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