Spatial Distribution of DNA Double-Strand Breaks from Ion Tracks
Collection title:
Ion Beam Science
Collection subtitle:
solved and unsolved problems ; invited lectures presented at a symposium arranged by the Royal Danish Academy fo Sciences and Letters, Copenhagen, 1 - 5 May 2006. Band 1
Collection editors:
Sigmund, Peter
Series title:
Matematisk-fysiske Meddelelser
Series volume:
52
Place of publication:
Kopenhagen
Publishing institution:
Kongelige Danske Videnskabernes Selskab
Publisher:
Royal Danish Academy of Sciences and Letter
Year:
2006
Pages from - to:
59-85
Language:
Englisch
Abstract:
Theoretical and experimental approaches are developed to investigate the spatial distribution of DNA damage induced by energetic ions in cell nuclei, with a special emphasis on DNA double-strand breaks (DSB). Using a phenomenological description for the relationship between energy dose and DSB induction, the total number of DSBs and their average number per unit pathlength can be calculated analytically for single ion tracks in cell nuclei. A simple approach to microscopic DNA damage description is offered by analytical representations which give the average energy dose in dependence of the radial distance from the ion track. However, the extreme fluctuations in the DNA damage per volume, which is due to the inhomogeneous ionisation events of the individual secondary electron paths and the structure of chromatin in the nucleus, make a true follow-up of the ionisation and excitation events desirable, e.g. by using Monte Carlo methods. The visualisation of DSBs by staining proteins which accumulate in large amounts at DSB repair sites, thus forming so-called foci, allows to analyse the spatial distribution of DSB sites under the fluorescence microscope. With this method, generally a much lower number of DSB sites along an ion track is observed than expected on basis of calculations. This observation hints at insufficient consideration of gross structures in the organisation of nuclear DNA or at a fast clustering of DSBs, possibly to form repair factories. «
Theoretical and experimental approaches are developed to investigate the spatial distribution of DNA damage induced by energetic ions in cell nuclei, with a special emphasis on DNA double-strand breaks (DSB). Using a phenomenological description for the relationship between energy dose and DSB induction, the total number of DSBs and their average number per unit pathlength can be calculated analytically for single ion tracks in cell nuclei. A simple approach to microscopic DNA damage description... »