Constraints on Energy Deposition and Target Size of Multiply Damaged Sites Associated with DNA Double-strand Breaks

David J. Brenner, John F. Ward

International Journal of Radiation Biology · 1992 · 273 citations · 52 references

Concepts

TL;DR

Heavy‑ion and α‑particle experiments provide trends that enable quantitative comparisons with calculations. The study proposes using experimental dsb yield data across radiation qualities to constrain the energy‑deposition mechanisms responsible for DNA double‑strand breaks. Track‑structure simulations identify ionization clusters whose frequency correlates with dsb relative biological effects, linking cluster size to biological impact. LMDS causing dsb likely involve 2–5 ionizations within 1–4 nm diameters, and these cluster size estimates are robust despite data and simulation uncertainties.

Abstract

We suggest that the observed experimental data on relative double-strand break (dsb) yield as a function of radiation quality can act as valuable constraints in defining the type of energy deposition which causes this basic lesion in radiation biology. Both heavy-ion and α-particle data show sufficient trends for quantitative comparisons with calculation to be made. We use the technique of track-structure simulation and search for energy-deposition clusters (containing at least a given number of ionizations in a given diameter) whose relative frequencies (compared to sparsely ionizing radiation) correlate with the relative biological effects (RBEs) for dsb induction. We conclude that locally multiply damaged sites (LMDS) which cause dsb are probably energy depositions of at least two to five ionizations localized, respectively, in sites of diameters of 1–4 nm. Although our derived cluster sizes should be viewed in light of the quality of the experimental data and uncertainties in the computer simulations at the nanometre level, it is unlikely that these estimates of cluster sizes would change greatly.

References

52