Extrapolation of the DNA fragment-size distribution after high-dose irradiation to predict effects at low doses

The patterns of DSBs induced in the genome are different for sparsely and d ensely ionizing radiations: In the former case, the patterns are well descr ibed by a random-breakage model; in the latter, a more sophisticated tool i s needed. We used a Monte Carlo algorithm with a random-walk geometry of ch romatin, and a track structure defined by the radial distribution of energy deposition from an incident ion, to fit the PFGE data for fragment-size di stribution after high-dose irradiation. These fits determined the unknown p arameters of the model, enabling the extrapolation of data for high-dose ir radiation to the low doses that are relevant for NASA space radiation resea rch. The randomly-located-clusters formalism was used to speed the simulati ons. It was shown that only one adjustable parameter, Q, the track efficien cy parameter, was necessary to predict DNA fragment sizes for wide ranges o f doses. This parameter was determined for a variety of radiations and LETS and was used to predict the DSB patterns at the HPRT locus of the human X chromosome after low-dose irradiation. It was found that high-LET radiation would be more likely than low-LET radiation to induce additional DSBs with in the HPRT gene if this gene already contained one DSB. (C) 2001 by Radiat ion Research Society.