CLUSTERS OF DNA-DAMAGE INDUCED BY IONIZING-RADIATION - FORMATION OF SHORT DNA FRAGMENTS .1. THEORETICAL MODELING

We have developed a general theoretical model for the interaction of i onizing radiation with chromatin. Chromatin is modeled as a 30-nm-diam eter solenoidal fiber composed of 20 turns of nucleosomes, 6 nucleosom es per turn. Charged-particle tracks are modeled by partitioning the e nergy deposition between primary track core, resulting from glancing c ollisions with 100 eV or less per event, and delta rays due to knock-o n collisions involving energy transfers >100 eV. A Monte Carlo simulat ion incorporates damages due to the following molecular mechanisms: (1 ) ionization of water molecules leading to the formation of . OH, . H, e(aq), etc.; (2) . OH attack on sugar molecules leading to strand bre aks; (3) . OH attack on bases; (4) direct ionization of the sugar mole cules leading to strand breaks; (5) direct ionization of the bases. Ou r calculations predict significant clustering of damage both locally, over regions up to 40 bp and over regions extending to several kilobas e pairs. A characteristic feature of the regional damage predicted by our model is the production of short fragments of DNA associated with multiple nearby strand breaks. The shapes of the spectra of DNA fragme nt lengths depend on the symmetries or approximate symmetries of the c hromatin structure. Such fragments have subsequently been detected exp erimentally and are reported in an accompanying paper (B. Rydberg, Rad iat. Res. 145, 200-209, 1996) after exposure to both high- and low-LET radiation. The overall measured yields agree well quantitatively with the theoretical predictions. Our theoretical results predict the exis tence of a strong peak at about 85 bp, which represents the revolution period about the nucleosome. Other peaks at multiples of about 1,000 bp correspond to the periodicity of the particular solenoid model of c hromatin used in these calculations. Theoretical results in combinatio n With experimental data on fragmentation spectra may help determine t he consensus or average structure of the chromatin fibers in mammalian DNA. (C) 1996 by Radiation Research Society.