The structure of chromatin at the level of the 30 nm fibre has been studied in considerable detail, but little is
known about how this fibre is arranged within the interphase chromosome territory. Over the years, various
polymer models were developed to simulate chromosome structure, for example the random-walk/giant-loop
(RWGL) model, the multi-loop subcompartment (MLS) model, and the interconnected-fibre-loop model
(Friedland et al., 1999). These models differ mainly in the size and arrangement of the chromatin loops and,
correspondingly, in the predicted distribution of chromatin density within the nucleus. It occurred to us that
densely ionising radiation can be used to probe the actual distribution of chromatin density in human interphase
cells. In contrast to sparsely ionising radiation (e.g. X-rays), which induces DNA double-strand breaks (DSB)
that are distributed randomly within the nucleus, irradiation with densely ionising accelerated ions leads to
spatial clustering of DSB. This inhomogeneity in DSB localisation, together with an inhomogeneity of DNA
density within the nucleus, causes an over-dispersion in the resulting distribution of DNA fragment sizes that can
be detected by pulsed-field gel electrophoresis.
Using the above-mentioned chromosome models, we performed computer simulations to predict the DNA
fragment size distributions resulting from irradiation with accelerated ions, and compared the predicted
distributions with those obtained experimentally. We found that simulations based on the MLS model, in which
local variations in chromatin density are higher than in the other models, resulted in the best agreement between
calculation and experiment
