Effects of track structure and cell inactivation on the calculation of heavy ion mutation rates in mammalian cells

Abstract

Abstract. It has long been suggested that inactivation severely effects the probability of mutation by heavy ions in mammalian cells. Heavy ions have observed cross sections of inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. In the track structure model of Katz the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated using the dose-response of the system to 7-rays and the radial dose of the ions and may be equal to unity at small impact parameters for some ions. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT mutations in Chinese hamster cells and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability of mutation by relativistic heavy ions due to the radial extension of ions track from 6-rays in agreement with the microlesion concept. The effects of inactivation on mutations rates make it very unlikely that a single parameter such as LET or z*'/p2 can be used to specify radiation quality for heavy ion bombardment.

Radial distribution of electron spectra from high-energy ions

“…The secondary electron spectrum for the LZE ions is softer, both at small radial distances and at the maximal radial distances where the highest energy ejected electrons are stopped (electron track-ends). However, for large target volumes including a response dependent on alterations in spatially distributed target molecules, the present energy deposition model [6,7] predicts that the effects of track width increase the effectiveness of HZE ions over LZE ions.…”

“…For over 30 years, the average or amorphous track model has successfully described the response of a wide variety of physical detectors and biological systems to heavy particle irradiation using the radial dose distribution from delta-rays about the path of the ion as the key physical descriptor [4][5][6][7][8]. In some instances, the response of physical or biological systems may have a dependence on electron energy other than the electron linear energy transfer (LET).…”

Applications of amorphous track models in radiation biology

“…The IGK model has considered mutations in mammalian cells [51], including the effects of inactivation on single-track action. The recognition of the effects of inactivation on mutation yields has been discussed in biophysical models for many years [52].…”

“…The recognition of the effects of inactivation on mutation yields has been discussed in biophysical models for many years [52]. The IGK calculations described such effects by modelling the track-structure effect resulting from the spatial distribution of targets for inactivation and mutation [51]. For predicting mutation effects, the dose response for gamma rays, P M , is considered along with the probability of expression of the mutation as determined by P I .…”

“…Comparisons of calculation [51] to experiments [43][44][45][46] for HPRT mutation in V79 cells are shown in Fig. 3b.…”