Polymer Chromosome Models and Monte Carlo Simulations of Radiation Breaking
DNA
A. L. Ponomarev, R. K. Sachs
Department of Mathematics, University of California, Berkeley,
CA 94720, USA
Date:
Abstract:
Motivation: Chromatin breakage by ionizing radiation is relevant
to studies of carcinogenesis, tumor radiotherapy, biodosimetry and molecular
biology. This article focuses on computer analysis of chromosome irradiation
in mammalian cells. Methods: Polymer physics and Monte Carlo numerical methods
are used to develop a coarse-grained computational approach. Chromatin
is modeled as a random walk on a cubic lattice, and the radiation tracks
hitting the chromatin are modeled as straight lines hitting lattice sites.
Each track can make a cluster of DSBs1
on a chromosome. Results: The results obtained replace conjectured DNA fragment-size
distribution functions in the recently developed RLC1 formalism
by more mechanistically motivated distributions. The discrete lattice algorithm
reproduces features of current radiation experiments relevant to chromatin
on large scales. It approximates the continuous formalism and experimental
data with adequate precision. It was also found that assuming either fixed
chromatin with correlations among different clusters of DSBs or moving
chromatin with no such correlations gives virtually identical numerical
predictions. Availability: This set of subroutines comprises the DNABreak
package available at the UC Berkeley mathematical radiobiology site: /sachs/ponomarev.html