Computer Simulation of Data on Chromosome Aberrations Produced by X Rays or Alpha Particles and Detected by Fluorescence In Situ Hybridization

Abstract

With fluorescence in situ hybridization (FISH), many different categories of chromosome aberrations can be recognized-dicentrics, translocations, rings and various complex aberrations such as insertions or three-way interchanges. Relative frequencies for the various aberration categories indicate mechanisms of radiation-induced damage and reflect radiation quality. Data obtained with FISH support a proximity version of the classic random breakage-and-reunion model for the formation of aberrations. A Monte Carlo computer implementation of the model, called the CAS (chromosome aberration simulator), is generalized here to high linear energy transfer (LET) and compared to published data for human cells irradiated with X rays or 238Pu alpha particles. For each kind of radiation, the CAS has two adjustable parameters: the number of interaction sites per cell nucleus and the number of reactive double-strand breaks (DSBs) per gray. Aberration frequencies for various painted chromosomes, of varying lengths, and for 11 different categories of simple or complex aberrations were simulated and compared to the data. The optimal number of interaction sites was found to be approximately 13 for X irradiation and approximately 25 for alpha-particle irradiation. The relative biological effectiveness (RBE) of alpha particles for the induction of reactive DSBs (which are a minority of all DSBs) was found to be approximately 4. The two-parameter CAS model adequately matches data for many different categories of aberrations. It can use data obtained with FISH for any one painting pattern to predict results for any other kind of painting pattern or whole-genome staining, and to estimate a suggested overall numerical damage indicator for chromosome aberration studies, the total misrejoining number.