Radiation damage on sub-cellular scales: beyond DNA

Abstract

This study investigates a model cell as a target for low-dose radiation using Monte Carlo simulations. Mono-energetic electrons and photons are used with initial energies between 10 and 50 keV, relevant to out-of-field radiotherapy scenarios where modern treatment modalities expose relatively large amounts of healthy tissue to low-dose radiation, and also to microbeam cell irradiation studies which show the importance of the cytoplasm as a radiation target. The relative proportions of number of ionizations and total energy deposit in the nucleus and cytoplasm are calculated. We show that for a macroscopic dose of no more than 1 Gy only a few hundred ionizations occur in the nucleus volume whereas the number of ionizations in the cytoplasm is over a magnitude larger. We find that the cell geometry can have an appreciable effect on the energy deposit in the cell and can cause a nonlinear increase in energy deposit with cytoplasm density. We also show that changing the nucleus volume has negligible effect on the total energy deposit but alters the relative proportion deposited in the nucleus and cytoplasm; the nucleus volume must increase to approximately the same volume as the cytoplasm before the energy deposit in the nucleus matches that in the cytoplasm. Additionally we find that energy deposited by electrons is generally insensitive to spatial variations in chemical composition, which can be attributed to negligible differences in electron stopping power for cytoplasm and nucleus materials. On the other hand, we find that chemical composition can affect energy deposited by photons due to non-negligible differences in attenuation coefficients. These results are of relevance in considering radiation effects in healthy cells, which tend to have smaller nuclei. Our results further show that the cytoplasm and organelles residing therein can be important targets for low-dose radiation damage in healthy cells and warrant investigation as much as the conventional focus of a high-dose radiation DNA target in tumour cells.

Nanoscale radiation transport and clinical beam modeling for gold nanoparticle dose enhanced radiotherapy (GNPT) using X-rays

“…It has to be noted that the mathematical framework of GNP-LQ could also be used in combination with other cell survival models than the LQ, for instance radiochemical models, 64 and that the computation of energy deposition may require MC simulation using specific cell geometry. [68][69][70] Finally, it has to be underlined that GNP-LQ applied to GNPT may not be directly applicable to proton/ion RT and discussing this issue is beyond the scope of this review.…”

“…For convenience, we arrange the literature according to the following order: general radiation transport aspects relevant for nanoscale simulations, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] macroscopic dose enhancement in contrast agents and dose perturbation at high-Z material interfaces, radiation transport for nanoscopic dose enhancement of GNP, [46][47][48][49][50][51][52][53][54][55][56][57][58] radiobiological and clinical aspects of GNPT, [59][60][61][62][63][64][65][66][67] application of Monte Carlo (MC) simulations to cellular environment, [68][69][70] modification of linear accelerator spectra to maximize dose enhancement 71 and GNPT using other than X-ray therapeutic beams (proton, electron). …”

Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol

“…Our results suggest that even if GNPs do not accumulate within the mitochondria, nanoparticles in close proximity to the organelle could still enhance damage due to the delocalisation of photoelectrons from the cytosol. Furthermore, a model that fully encapsulates the effects of radiation on the whole cell, not just the nuclear DNA, is essential for advancing our current understanding of the biological outcomes of irradiated cells (Waldren 2004, Baverstock & Belyakov 2005, Prise et al 2005, McMahon et al 2013, Byrne et al 2013, Kuncic et al 2012). …”

Computational Cell Dosimetry for Cancer Radiotherapy and Diagnostic Radiology

“…The importance of microscopic cell constituents such as the cytoplasm and nucleus as targets for radiation-induced cell damage has motivated recent studies using MC techniques to calculate doses to cellular targets, moving away from traditional waterbased calculations to MC models with varying levels of detail. 35,[53][54][55][56] Enger et al 55 modelled a single 7 μm-radius spherical 'nucleus' cavity in a homogeneous tissue cube.…”

“…Byrne et al 56 modelled the nucleus and cytoplasm as two concentric spheres (radii 2 and 5 μm) suspended in water. Thomson et al 35 developed multicellular, microscopic tissue structure models using spherical cells (nucleus and cell radii 5 and 7.35 μm, respectively), a range of elemental compositions, and a cell number density typical of cancerous tissues, demonstrating the sensitivity of cell doses to surrounding cells and extracellular matrix (ECM).…”