Frequent topic of debate since early work in the éeld Purpose: To investigate whether radiation-induced misrejoin- (Sax 1938, 1940). Misrejoined breakpoints are an ing of chromosome breakpoints is randomly or non-randomly easily detected manifestation of radiation exposure, distributed throughout the human genome. and therefore many research groups have used these Materials and methods: Data were combined from as many pub- events as an endpoint in human biodosimetry studies. lished cytogenetic studies as possible. The percentage of radi- ation-induced breaks per megabase (Mb) of DNA between all However, due to the time-consuming nature and human chromosomes was calculated, and the observed and potential subjectivity of chromosome banding tech- expected numbers of breakpoints based on DNA content between niques and the lack of a suæcient number of diå erent and within chromosomes were compared. èuorescent stains when using chromosome painting Results: A DNA-proportional distribution of breakpoints in 14 (without image processing), it has become common autosomes and a statistically signiécant deviation from propor- tionality in the other eight autosomes and the sex chromosomes practice to analyse only one or a few chromosomes. was found. Regression analysis showed no signiécant change in These analyses of a subset of chromosomes result in breakpoint frequency per Mb of DNA relative to autosome size. conclusions that are primarily related to the chromo- Analysis between chromosome arms showed a non-random somes under analysis, although the data are often distribution of induced breakpoints within certain autosomes, extrapolated to yield estimates of the overall genomic particularly the acrocentrics. In cases of non-random distribu- tions, a prevalence of events was found at heterochromatic frequency of chromosome exchanges. If this extra- regions and/or telomeres, and a clustering of breakpoints was polation is to be feasible, it must be assumed that found near the centromeres of many chromosomes. the chromosomes analysed are representative of the Conclusions: There is an approximately linear proportionality genome as a whole. This assumption requires that between autosomal DNA content and observed breakpoint radiation-induced chromosome rearrangements are number, suggesting that subsets of autosomes can be used to estimate accurately the overall genomic frequency of misrejoined randomly distributed throughout the genome and breakpoints contingent upon a carefully selected subset. depend mainly on DNA content. However, this conclusion may not apply to the sex chromosomes. Over the years numerous studies have been per- The results also support the inèuence of chromatin organization formed to address the assumption of a chromosome and/or preferential DNA repair/misrejoining on the distribution size distribution of radiation-induced chromosome of induced breakpoints. However, these eå ects are not suæcient at a global level to dismiss the value of cytogenetic analysis using breakpoints in human cells. These include both a genome subset for biodosimetry.