Details of Grant 

EPSRC Reference:	GR/S56276/01
Title:	The influence of high Z atoms on the generation of complex DNA lesions by ionizing radiation: implications for radiotherapy
Principal Investigator:	Latimer, Professor C
Other Investigators:	Shah, Dr M Currell, Professor F
Researcher Co-Investigators:
Project Partners:
Department:	Sch of Mathematics and Physics
Organisation:	Queen's University of Belfast
Scheme:	Standard Research (Pre-FEC)
Starts:	26 April 2004	Ends:	25 September 2007	Value (£):	263,612
EPSRC Research Topic Classifications:	Medical science & disease Scattering & Spectroscopy
EPSRC Industrial Sector Classifications:	Healthcare
Related Grants:	GR/S56283/02
Panel History:
Summary on Grant Application Form
Radiotherapy remains one of the most effective forms of cancer treatment. Ionisation, leading to DNA strand breaks is one of the dominant energy absorption mechanisms for radiation of this quality. A small proportion of these breaks are not accurately repaired and result in death of cancer cells. Irradiation with heavy charged particles deposits a large amount of energy in a small volume, generating multiply-damaged sites, which are very poorly repaired and are thus highly cytotoxic. However, heavy ion beam generators are hugely expensive and currently impractical for routine clinical use, but we believe it may be possible to enhance the generation of multiply-damaged sites in DNA by a simpler mechanism. If atoms with high atomic number (Z) could be preferentially localised within tumours, their large cross section would result in multiple ionisation within a small volume. As the space charge of the multiply ionised sites can induce large amounts of Coulomb repulsion force within DNA molecules, substantial strand/bond breakage can ensue as charged fragments fly away from the sites. This would result in highly efficient cell killing and would complement the spatial targeting that is an inherent advantage of radiotherapy. Our aim is to gain an understanding of the molecular events resulting from DNA irradiation in the presence or absence of atoms with a range of (high) Z values. We will use a variety of techniques, including pulsed field gell electrophoresis and atomic force microscopy to investigate the nature of these lesions and correlate the findings with analyses of ejected molecular species using time of flight mass spectroscopy. The results obtained will be used to inform future developments of this approach in vitro and in vivo.
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Organisation Website:	http://www.qub.ac.uk