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There is an approximately linear proportionality between autosomal DNA content and observed breakpoint number, suggesting that subsets of autosomes can be used to estimate accurately the overall genomic frequency of misrejoined breakpoints contingent upon a carefully selected subset. However, this conclusion may not apply to the sex chromosomes. The results also support the influence of chromatin organization and/or preferential DNA repair/misrejoining on the distribution of induced breakpoints. However, these effects are not sufficient at a global level to dismiss the value of cytogenetic analysis using a genome subset for biodosimetry.

A Monte Carlo simulation computer program for radiation-produced chromosome aberrations, based on the breakage-and-reunion model, was extended to include proximity effects due to localization of chromosomes and limited range for break-break interactions. Two adjustable parameters were used. One corresponds to total dose: the other determines proximity effects by specifying the number of 'interaction regions' in a cell nucleus. The use of additional adjustable parameters was avoided by assuming randomness of break induction and aberration production. FISH chromosome painting data were obtained from 1.9 Gy 60Co 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 were scored. An estimated average dsb-dsb interaction distance, based on 13 interaction regions, is about 1.3 micron. Monte Carlo methods give useful quantitative estimates of relative aberration yields, with a minimum of adjustable parameters and the theoretical assumptions, and indicated 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-genome aberration frequencies.

Radon is by far the most important contributor to the collective dose equivalent. Most of what is known about the hazards of radon daughters comes from epidemiological studies of miners. There are a few well defined areas in which in vitro research can complement such studies: First, more data on the relative effects of differing energy (LET) alpha-particles would help: (1) understand the significance of the depth of sensitive cells in the bronchial epithelium--which varies between individuals, as well as between smokers and non-smokers, and between miners and non-miners; (2) understand the relative hazards of radon and thoron daughters. Second, reliable methods for predicting high LET responses from low LET response, would enable Japanese A-bomb survivor data to be applied with confidence. Third, understanding the effects of single-particle traversals of cells relative to multiple traversals could allow reliable extrapolation of epidemiological miner data to low exposures. Fourth, a better understanding of the nature of the interaction between tobacco and radiation damage would help predict the effect of radon on non-smokers.

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