Relationship between radiation-induced aberrations in individual chromosomes and their DNA content: effects of interaction distance

Purpose: To study the effect of the interaction distance on the frequency o f inter- and intrachromosome exchanges in individual chromosomes with respe ct to their DNA content. Assumptions: Chromosome exchanges are formed by misrejoining of tw DNA doub le-strand breaks (DSB) induced within an interaction distance, d. It is ass umed that chromosomes in G(o)/G(1) phase of the cell cycle occupy a spheric al domain in a cell nucleus, with no spatial overlap between individual chr omosome domains. Results: Formulae are derived for the probability of formation of inter-, a s well as intra-, chromosome exchanges relating to the DNA content of the c hromosome for a given interaction distance. For interaction distances <1 <m u>m, the relative frequency of interchromosome exchanges predicted by the p resent model is similar to that by Cigarran et al. (1998) based of the assu mption that the probability of interchromosome exchanges is proportional to the 'surface area' of the chromosome territory. The 'surface area' assumpt ion is shown to be a limiting case of d-->0 in the present model. The prese nt model also predicts that the probability of intrachromosome exchanges oc curring in individual chromosomes is proportional to their DNA content with correction terms. Conclusion: When the interaction distance is small, the 'surface area' dist ribution for chromosome participation in interchromosome exchanges has been expected. However, the present model shows that for the interaction distan ce as large as 1 mum, the predicted probability of interchromosome exchange formation is still close to the surface area distribution. Therefore, this distribution does not necessarily rule out the formation of complex chromo somal aberrations by long-range misrejoining of DSB.