Chromosome Aberration and Mutation Frequencies Induced by Low Doses and Low Fluencies of Ionizing Radiation

Aloke Chatterjee and William Holley

We have developed a general theoretical model which describes the interactions of charged particles (electrons and iron particles) with DNA in the form of chromatin fibers organized into chromosomes and the cellular nucleus. The chromosomes are modeled as polymers consisting of short segments of 30 nm chromatin fiber randomly organized into loops of various sizes, ranging from a few kbp to greater than 100 kbp. To simulate the whole human nucleus we pack 46 chromosomes of appropriate length into spheroidal volumes approximating that of the human nucleus. For each dose studied the appropriate number of particle tracks are generated and allowed to penetrate the nucleus randomly in three dimensions and interact with the DNA. Our calculated yields of initial damages of different types agree well with experimental measurements for electrons as well as iron particles. We are studying the induction by ionizing radiation of large and intermediate scale genomic rearrangements (deletions, translocations, etc.) based on various hypotheses for the faithful and strand breaks. Calculations can be performed at all dose levels, in particular, down to levels of one cGy or less. By incorporating time dependence into the production and repair of DNA damage we are able to study both low dose and low dose rate effects. Results of calculations of inter- and intra- chromosomal rearrangements as well as gene specific mutations will be presented.