Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Abstract

Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.

Coupling Radiation Transport and Track-Structure Simulations: Strategy Based on Analytical Formulas Representing DNA Damage Yields

“…The present work complements the analysis of our previous study [16], where DNA damage yields were parameterized as a function of particle LET in the cell nucleus. Parameterizing DNA damage in terms of particle energy rather than LET has several advantages: First, particle energy is more readily available from transport codes than LET in the restricted sense as obtained from PARTRAC track-structure simulations, i.e., as energy deposited to the cell nucleus per unit track length.…”

“…The basic mechanistic assumption that underpins the present coupling strategy is that the analyzed DNA damage is additive, i.e., that the yields of the studied damage classes upon a mixedfield irradiation are given by a sum of yields from individual tracks. Due to the local nature of DSBs, their clusters and sites, this assumption is fulfilled up to doses of the order of several hundred Gy [16,35]: The probability that, e.g., two DSBs induced by different primary particles would combine into a DSB cluster is negligible, since the two DSBs would have to occur within 25 bp. The same argument holds even stronger for a combination of two strand breaks into a DSB, which would have to take place within 10 bp.…”

“…In this work, we have analyzed the previously published comprehensive database of PARTRAC simulations on DNA damage induced by light ions [20,21]. Model cell nuclei were irradiated by 1 H, 4 He, 7 Li, 9 Be, 11 B, 12 C, 14 N, 16 O or 20 DSBs, DSB clusters and DSB sites were scored. From absolute numbers of the lesions and the deposited dose, damage yields per Gy per Gbp were calculated.…”

“…The high-energy (i.e., low-LET) behavior was taken from Ref. 16, using the following values: p 0 6.8 DSB, 0.07 DSB clusters, and 6.8 DSB sites per Gy per Gbp. Parameters of these test functions were fitted to the results of track-structure simulations using non-linear model fitting in Matlab (The MathWorks Inc., United States).…”

“…As such, it could be argued that they are ideal to characterize the radiation field in a single cell nucleus that can be assumed as a quasi-spherical volume with a linear dimension of ∼10 µm. These considerations are at the basis of our previous works, in which we proposed a full coupling between PHITS and PARTRAC to derive the RBE of neutrons of different energy [14,15], as well as a full set of analytical functions [16] reproducing PARTRAC results on different types of DNA damage as a function of an LET estimate, when the cell nucleus is irradiated with a variety of light ions at radiotherapy-relevant energies down to stopping. Such LET estimate, obtained by dividing the dose delivered to the cell nucleus by particle fluence (with appropriate conversion of units), is indeed analogous to the concept of the dose-mean lineal energy in microdosimetry.…”