Locations of radiation-produced DNA double strand breaks along chromosomes: a stochastic cluster process formalism

Ionizing radiation produces DNA double strand breaks (DSBs) in chromosomes. For densely ionizing radiation, the DSBs are not spaced randomly along a c hromosome: recent data for size distributions of DNA fragments indicate bre ak clustering on kbp-Mbp scales. Different DSB clusters on a chromosome are typically made by different, statistically independent, stochastically str uctured radiation tracks, and the average number of tracks involved can be small. We therefore model DSB positions along a chromosome as a stationary Poisson cluster process, i.e. a stochastic process consisting of secondary point processes whose locations are determined by a primary point process t hat is Poisson, Each secondary process represents a break cluster, typicall y consisting of 1-10 DSBs in a comparatively localized stochastic pattern d etermined by chromatin geometry and radiation track structure. Using this P oisson cluster process model, which we call the randomly located clusters ( RLC) formalism, theorems are derived for how the DNA fragment-size distribu tion depends on radiation dose. The RLC dose-response relations become non- linear when the dose becomes so high that DSB clusters from different track s overlap or adjoin closely. The RLC formalism generalizes previous models, fits current data adequately and facilitates mechanistically based extrapo lations from high-dose experiments to the much lower doses of interest for most applications. (C) 1999 Elsevier Science Inc, All rights reserved.