The role of lysosomes in radiation induced genomic instability
type: CreativeWork
description: Our understanding of ionizing radiation and its associated biological effects has recently under- gone a paradigm shift from a DNA-centric model to one inclusive of non-targeted effects (NTE), so called for the lack of direct radiation interaction with DNA. Two effects encompassed within the NTE paradigm are termed genomic instability (GI) and bystander effects (BE). GI can be described as an increase in rate of genetic alterations many cell generations after the initial radi- ation exposure. BE can be defined as the manifestation of radiation like effects in un-irradiated cells that have communicated with cells that have been irradiated either through inter-signalling utilising gap junctions or the secretion of a soluble diffusion signalling factor. The exact mechanisms that underlie these processes are still under investigation but a wealth of evidence suggests that a number of mechanisms are involved. These include; cytokine signalling, oxidative stress, inflammation and sub-cellular alterations, in addition to factors such as genetic background and radiation quality/dose. This study was designed to investigate lysosomal involvement in radiation induced NTE, whether it be downstream of one of the above mentioned mechanisms, or independent of their involve- ment. To this end the primary human fibroblast cell line, HF19, was exposed to X-rays at therapeutic and diagnostic doses of 2 and 0.1 Gy respectively. Bystander groups were also established by media transfer techniques. Cells were analysed over the first 24 hours and then at 1 and 20 population doublings, initially for detection of GI and BE and thus confirm the suitability of the system. The lysosomes were then analysed for permeability and their distri- bution within the cell. Oxidative stress was also measured in a bid to correlate this event with lysosomal perturbations. Finally lysosomal contents, in particular DNaseIIα, were analysed for their cellular location along with analysis of nuclear membrane per…
abstract: Our understanding of ionizing radiation and its associated biological effects has recently under- gone a paradigm shift from a DNA-centric model to one inclusive of non-targeted effects (NTE), so called for the lack of direct radiation interaction with DNA. Two effects encompassed within the NTE paradigm are termed genomic instability (GI) and bystander effects (BE). GI can be described as an increase in rate of genetic alterations many cell generations after the initial radi- ation exposure. BE can be defined as the manifestation of radiation like effects in un-irradiated cells that have communicated with cells that have been irradiated either through inter-signalling utilising gap junctions or the secretion of a soluble diffusion signalling factor. The exact mechanisms that underlie these processes are still under investigation but a wealth of evidence suggests that a number of mechanisms are involved. These include; cytokine signalling, oxidative stress, inflammation and sub-cellular alterations, in addition to factors such as genetic background and radiation quality/dose. This study was designed to investigate lysosomal involvement in radiation induced NTE, whether it be downstream of one of the above mentioned mechanisms, or independent of their involve- ment. To this end the primary human fibroblast cell line, HF19, was exposed to X-rays at therapeutic and diagnostic doses of 2 and 0.1 Gy respectively. Bystander groups were also established by media transfer techniques. Cells were analysed over the first 24 hours and then at 1 and 20 population doublings, initially for detection of GI and BE and thus confirm the suitability of the system. The lysosomes were then analysed for permeability and their distri- bution within the cell. Oxidative stress was also measured in a bid to correlate this event with lysosomal perturbations. Finally lysosomal contents, in particular DNaseIIα, were analysed for their cellular location along with analysis of nuclear membrane per…
author: Bright, Scott J.
language: en
date published: 2013
date modified: 2026-07-24T03:43:16Z
provider: Oxford Brookes University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Oxford Brookes University