RADIATION-INDUCED CHROMOSOME INSTABILITY AND INTERCELLULAR COMMUNICATION: THE ROLE OF DOSE RATE AND IMPLICATIONS FOR CARCINOGENESIS
type: CreativeWork
description: The biological risks associated with low dose and low dose rate (LDR) radiation exposures are not yet well characterised. Experimental studies indicate that in addition to biological effects resulting from direct DNA damage, a variety of non-DNA targeted effects (NTE) including radiation-induced genomic instability (RIGI), genomic instability being a known enabling characteristic of cancer, may crucially contribute to the overall outcome. RIGI can induce delayed mutations, chromosomal damage and micronucleus formation in the progeny of cells many generations after the original radiation event. The work presented explores the role of dose and dose rate, as well as radiation quality, on RIGI. For low-LET x-rays, the induction of RIGI in normal primary human fibroblast (HF19) cells was investigated as a function of dose and dose rate and as a function of dose for high-LET alpha-particles. An additional aim was to investigate the potential role of reactive oxygen species (ROS), tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β1) in the induction of DNA damage and GI in HF19 cells following 0.1 and 1 Gy high dose rate (HDR) and low dose rate (LDR) x-ray irradiation. The x-ray data clearly show early DNA damage and RIGI many population doublings (PD) after exposure, not only after high dose and high dose rate exposures, but also at similar levels following low dose and low dose rate exposures. 0.1 Gy and 1 Gy LDR x-ray groups suggested more damage compared to the corresponding HDR groups. However, at 20 PD the HDR groups suggested higher induction of DNA damage compared to the equivalent LDR x-ray irradiation groups. A higher induction of ROS following 0.1 and 1 Gy LDR and HDR x-ray was also demonstrated providing a potential mechanism for induction of DNA damage and RIGI. The alpha-particle results indicate significant induction of early DNA damage and RIGI at 10 and 20 PD at doses down to 0.001 Gy, reducing at lower doses. At these low dose…
abstract: The biological risks associated with low dose and low dose rate (LDR) radiation exposures are not yet well characterised. Experimental studies indicate that in addition to biological effects resulting from direct DNA damage, a variety of non-DNA targeted effects (NTE) including radiation-induced genomic instability (RIGI), genomic instability being a known enabling characteristic of cancer, may crucially contribute to the overall outcome. RIGI can induce delayed mutations, chromosomal damage and micronucleus formation in the progeny of cells many generations after the original radiation event. The work presented explores the role of dose and dose rate, as well as radiation quality, on RIGI. For low-LET x-rays, the induction of RIGI in normal primary human fibroblast (HF19) cells was investigated as a function of dose and dose rate and as a function of dose for high-LET alpha-particles. An additional aim was to investigate the potential role of reactive oxygen species (ROS), tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β1) in the induction of DNA damage and GI in HF19 cells following 0.1 and 1 Gy high dose rate (HDR) and low dose rate (LDR) x-ray irradiation. The x-ray data clearly show early DNA damage and RIGI many population doublings (PD) after exposure, not only after high dose and high dose rate exposures, but also at similar levels following low dose and low dose rate exposures. 0.1 Gy and 1 Gy LDR x-ray groups suggested more damage compared to the corresponding HDR groups. However, at 20 PD the HDR groups suggested higher induction of DNA damage compared to the equivalent LDR x-ray irradiation groups. A higher induction of ROS following 0.1 and 1 Gy LDR and HDR x-ray was also demonstrated providing a potential mechanism for induction of DNA damage and RIGI. The alpha-particle results indicate significant induction of early DNA damage and RIGI at 10 and 20 PD at doses down to 0.001 Gy, reducing at lower doses. At these low dose…
author: Elbakrawy, Eman Mohammed Ahmed
language: en
date published: 2017
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

PropertyValue
property ID: DOI
value: 10.24384/dbgp-z219