Spatial Distribution of DNA Double-Strand Breaks from Ion Tracks
Titel Sammlung:
Ion Beam Science
Untertitel Sammlung:
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
Herausgeber Sammlung:
Sigmund, Peter
Reihentitel:
Matematisk-fysiske Meddelelser
Bandnummer Reihe:
52
Verlagsort:
Kopenhagen
Verlegende Institution:
Kongelige Danske Videnskabernes Selskab
Verlag:
Royal Danish Academy of Sciences and Letter
Jahr:
2006
Seiten von - bis:
59-85
Sprache:
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... »