153 Physica Medica - Vol. XVII, Supplement 1, 2001 Monte Carlo Predictions of DNA Fragment-Size Distributions for Large Sizes after HZE Particle Irradiation A.L. Ponomarev 1,* , F.A. Cucinotta 1 , R.K. Sachs 2 , D.J. Brenner 3 1. NASA Johnson Space Center, Mail Code SN, Houston, TX 77058 (USA) 2. Department of Mathematics, University of California, Berkeley, CA 94720 (USA) 3. Center for Radiolobical Research, Columbia University, New York, NY 10032 (USA) 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 ª 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 . This dose-independent parameter depends only weakly on LET. Multi-track, high-dose effects depend on the cluster intensity parameter l, proportional to fluence as defined by the RLC formalism. After l is determined by a numerical experiment, the model reduces to one adjustable parameter . The best numerical fits to the experimental data, determining , are obtained. The knowledge of l and  allows us to give biophysically based extrapolations of high-dose DNA fragment-size data to low doses or to high LETs. KEYWORDS: Polymer chromatin model, non-random DNA breakage. 1 st International Workshop on Space Radiation Research and 11 th Annual NASA Space Radiation Health Investigators’ Workshop Arona (Italy), May 27-31, 2000 * Corresponding Author: alponoma@ems.jsc.nasa.gov 1 Abbreviations: DSB = DNA double-strand break; DNAbreak = computer program based on a Monte Carlo algorithm for chromatin and its breakage by radiation tracks; PFGE = pulsed- field gel electrophoresis; LET = linear energy transfer; kbp = 10 3 base pairs; Mbp = 10 6 base pairs; RLC formalism = randomly-located-clusters formalism; HZE particles = high-LET ions in space environment. 1. Introduction High-LET 1 space radiation includes energetic, fully ionized heavy ions, whose number, when traversing a certain area, obeys Poisson statistics [1]. The traversal of tissue, however, is modified by atomic/ molecular energy-loss processes and nuclear reac- tions [2]. These high-LET ions are mostly Fe, but other nuclei, such as N, are also present. We focus on HZE particles because they induce non-random breakage in DNA, as the result of the sharp energy profile in a track [3, 4, 5]. Recent pulsed-field gel electrophoresis (PFGE) experiments at LET ª 100 keV/mm or more [6, 7, 8] measure the corresponding distributions of DNA frag- ment sizes, where ‘size’ is used, here and throughout, to mean DNA content. The ionizations due to one high-LET radiation track are spatially correlated, being predominantly near the line representing the center of the track rather than spread randomly over a whole cell nucleus. Localization of ionizations is determi- ned by the type of incident particles and leads to clustering of DSBs along chromosomes. A determi- stic model [4] of track structure will be used to cal- culate the profile of energy imparted to the cell inte- rior. Fig. 1 – DSB clustering along chromosome. Panel A depicts a chromosome represented by a random walk and tracks hitting the DNA volume (tracks that have missed DNA are not shown). Panel B is the locations of DSBs (stars) produced along the chromosome contour, shown as a line. In reality the picture of DSBs on Panel B is the result of juxtaposition of many DSB clusters produced by one track, examples of which are shown on Panel C. Subcluster multiplicities are given by numbers; one of the subclusters is resolved at the bottom of Panel C.