title: Monte Carlo predictions of DNA fragment-size distributions for large sizes after HZE particle irradiation.
abstract: DSBs (double-strand breaks) produced by densely ionizing space radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. DSB clustering at large scales, from >100 Mbp down to approximately 2 kbp, is modeled using a Monte-Carlo algorithm. A random-walk model of chromatin is combined with a track model, that predicts the radial distribution of energy from an ion, and the RLC (randomly-located-clusters) formalism, in software called DNAbreak. This model generalizes the random-breakage model, whose broken-stick fragment-size distribution is applicable to low-LET radiation. DSB induction due to track interaction with the DNA volume depends on the radiation quality parameter Q. This dose-independent parameter depends only weakly on LET. Multi-track, high-dose effects depend on the cluster intensity parameter lambda, proportional to fluence as defined by the RLC formalism. After lambda is determined by a numerical experiment, the model reduces to one adjustable parameter Q. The best numerical fits to the experimental data, determining Q, are obtained. The knowledge of lambda and Q allows us to give biophysically based extrapolations of high-dose DNA fragment-size data to low doses or to high LETs.
authors.affiliation: NASA Johnson Space Center, Houston, TX 77058, USA. alponoma@ems.jsc.nasa.gov
authors.forename: A L
authors.initials: AL
authors.lastname: Ponomarev
authors.forename: F A
authors.initials: FA
authors.lastname: Cucinotta
authors.forename: R K
authors.initials: RK
authors.lastname: Sachs
authors.forename: D J
authors.initials: DJ
authors.lastname: Brenner
mesh_terms: D000465:Algorithms; D000818:Animals; D016000:Cluster Analysis; D003359:Cosmic Radiation; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D007501:Iron; D016018:Least-Squares Analysis; D018499:Linear Energy Transfer; D008954:Models, Biological; D009010:Monte Carlo Method; D009584:Nitrogen; D011829:Radiation Dosage
chemical_list: D004247:DNA; D007501:Iron; D009584:Nitrogen