Rydberg, B., Heilbronn, L., Holley, W. R., Löbrich, M., Zeitlin, C., Chatterjee, A. and Cooper, P. K. Spatial Distribution and Yield of DNA Double-Strand Breaks Induced by 3–7 MeV Helium Ions in Human Fibroblasts. Radiat. Res. 158, 32–42 (2002).

Accelerated helium ions with mean energies at the target location of 3–7 MeV were used to simulate α-particle radiation from radon daughters. The experimental setup and calibration procedure allowed determination of the helium-ion energy distribution and dose in the nuclei of irradiated cells. Using this system, the induction of DNA double-strand breaks and their spatial distributions along DNA were studied in irradiated human fibroblasts. It was found that the apparent number of double-strand breaks as measured by a standard pulsed-field gel assay (FAR assay) decreased with increasing LET in the range 67–120 keV/μm (corresponding to the energy of 7–3 MeV). On the other hand, the generation of small and intermediate-size DNA fragments (0.1–100 kbp) increased with LET, indicating an increased intratrack long-range clustering of breaks. The fragment size distribution was measured in several size classes down to the smallest class of 0.1–2 kbp. When the clustering was taken into account, the actual number of DNA double-strand breaks (separated by at least 0.1 kbp) could be calculated and was found to be in the range 0.010–0.012 breaks/Mbp Gy^–1. This is two- to threefold higher than the apparent yield obtained by the FAR assay. The measured yield of double-strand breaks as a function of LET is compared with theoretical Monte Carlo calculations that simulate the track structure of energy depositions from helium ions as they interact with the 30-nm chromatin fiber. When the calculation is performed to include fragments larger than 0.1 kbp (to correspond to the experimental measurements), there is good agreement between experiment and theory.