Chromosome aberrations produced by ionizing radiation: Monte Carlo simulations and chromosome painting data

Monte Carlo simulations are used to analyze the reshuffling of chromosome segments which occurs when DNA is damaged by ionizing radiation. Programs are based on either Sax's classic breakage-and-reunion model or Revell's exchange model for chromosome aberrations. The simulations quantify the predictions of the two models in complete detail, using only one adjustable parameter which corresponds to total radiation dose. While testing subroutines, new analytic results on the chromosome/arm/break method of classifying aberrations were obtained. The model predictions were tested by using three-color fluorescence in situ hybridization (FISH) 'chromosome painting' on human lymphocyte cells irradiated with gamma-rays. Some of the per-cell aberration frequencies were observed to be intermediate between the predictions of the two models. This result indicates proximity 'effects', due to localization of chromosome interactions in space and time. Predictions based on chromosome arm lengths were found to be in good agreement with experiment. Monte Carlo simulations are a powerful, flexible way to compare models of chromosome aberration production with experiments quantitatively, using a minimum of theoretical presumptions.