The cytoplasm as a radiation target: an in silico study of microbeam cell irradiation

Abstract

We performed in silico microbeam cell irradiation modelling to quantitatively investigate ionisations resulting from soft x-ray and alpha particle microbeams targeting the cytoplasm of a realistic cell model. Our results on the spatial distribution of ionisations show that as x-rays are susceptible to scatter within a cell that can lead to ionisations in the nucleus, soft x-ray microbeams may not be suitable for investigating the DNA damage response to radiation targeting the cytoplasm alone. In contrast, ionisations from an ideal alpha microbeam are tightly confined to the cytoplasm, but a realistic alpha microbeam degrades upon interaction with components upstream of the cellular target. Thus it is difficult to completely rule out a contribution from alpha particle hits to the nucleus when investigating DNA damage response to cytoplasmic irradiation. We find that although the cytoplasm targeting efficiency of an alpha microbeam is better than that of a soft x-ray microbeam (the probability of stray alphas hitting the nucleus is 0.2% compared to 3.6% for x-rays), stray alphas produce more ionisations in the nucleus and thus have greater potential for initiating damage responses therein. Our results suggest that observed biological responses to cytoplasmic irradiation include a small component that can be attributed to stray ionisations in the nucleus resulting from the stochastic nature of particle interactions that cause out-of-beam scatter. This contribution is difficult to isolate experimentally, thus demonstrating the value of the in silico approach.

Geometrical structures for radiation biology research as implemented in the TOPAS-nBio toolkit

“…Spherical or elliptical cells are commonly used in Monte Carlo simulations (Byrne et al 2015, Douglass et al 2012, Incerti et al 2016, for example). Although spherical cells seem simplistic, there are many cases where spheroid cells effectively represent realistic cells, for example a lymphocyte in suspension (Rosenbluth et al 2006), some hepatoma cell lines (e.g., spherical FLC-4 cells (Laurent et al 2012)) or yeast cells (Jorgensen et al 2007).…”

Investigation of track structure and condensed history physics models for applications in radiation dosimetry on a micro and nano scale in Geant4

“…A common application of MC in radiation biology, and particularly nanodosimetry, is to calculate the ionisation cluster size distribution (ICSD) within a target of interest. This has been done for a variety of biological targets and radiation fields and using a variety of physical models, including both TS (Rabus and Nettelbeck 2011, Lazarakis et al 2012a, Burigo et al 2016 and CH approaches (Byrne et al 2015, McNamara et al 2016 and sometimes a combination of both types of models (Kuncic et al 2012, Douglass et al 2013. However, given the different approaches used by the different physics models it stands to reason that the ICSD will be somewhat dependent upon the chosen models.…”

Akt/mTOR mediated induction of bystander effect signaling in a nucleus independent manner in irradiated human lung adenocarcinoma epithelial cells

“…However, Byrne et al . suggest that the observed biological responses to cytoplasmic irradiation with microbeam X-rays or alpha particles could be attributed to a small amount of out-of-beam scattered ionizations in the nucleus [10]. As such, it is pertinent to carry out experiments with more unambiguous designs to study the RIBE induced by cytoplasm irradiation in order to better understand the mechanisms underlying the production and transduction of relevant RIBE signal(s).…”