PROXIMITY EFFECTS FOR CHROMOSOME-ABERRATIONS MEASURED BY FISH

A Monte Carlo simulation computer program for radiation-produced chrom osome aberrations, based on the breakage-and-reunion model, was extend ed to include proximity effects due to locailization of chromosomes an d limited range for break-break interactions. Two adjustable parameter s were used. One corresponds to total dose; the other determines proxi mity effects by specifying the number of 'interaction regions' in a ce ll nucleus. The use of additional adjustable parameters was avoided by assuming randomness of break induction and aberration production. FIS H chromosome painting data were obtained from 1.9 Gy Co-60 gamma-rays- irradiated human lymphocytes. The data were compared with the computer simulation results, taking individual chromosome lengths into account . With about 13 interaction regions, agreement between the experiment and the simulation was good, even when detailed categories of damage w ere scored. An estimated average dsb-dsb interaction distance, based o n 13 interaction regions, is about 1.3 mu m. Monte Carlo methods gave useful quantitative estimates of relative aberration yields, with a mi nimum of adjustable parameters and theoretical assumptions, and indica ted proximity effects. Computer simulation of FISH experiments can be adapted to any number of colours, any scoring criteria and any method of grouping aberrations into categories. Simulation allows systematic extrapolation of aberration data on painted chromosomes to whole-genom e aberration frequencies.