Does the Number of Irradiated Cells Influence the Spatial Distribution of Bystander Effects?

Abstract

There is growing evidence that the radiation effects at low doses are not adequately described by a simple linear extrapolation from high doses, due, among others, to bystander effects. Though several studies have been published on this topic, the explanation of the mechanisms describing the bystander effects remains unclear. This study aims at understanding how the bystander signals are or can be propagated in the cell culture, namely if the number of irradiated cells influences the bystander response. An A549 cell line was exposed to several doses of α-particles, being the bystander response quantified in two non-irradiated areas. The radius of irradiated areas differs by a factor of 2, and the non-irradiated areas were optimally designed to have the same number of cells. Our results show evidence for bystander effects occurring in cells far away from the irradiated ones, meaning that bystander signals can easily spread throughout the cell culture. Additionally, our study highlights that the damage caused by radiation on the surrounding of irradiated areas could be different according to the number of irradiated cells, i.e., for the same dose value; the overall cellular damage could be different.

Internal microdosimetry of alpha-emitting radionuclides

“…For example, the histogenesis of bone sarcoma after internal irradiation with alpha-emitters shows that the final histopathology of deterministic or stochastic endpoints depends on the microenvironment of a target cell, which has to be regarded as a synergistic morpho-functional tissue unit ("histion") (Goessner 2003). Furthermore, several non-targeted effects have been reported in the literature where cells hit by alpha particles induce a radiobiological response in non-irradiated neighboring cells (Sawant et al 2001;Fakir et al 2009;Belchior et al 2014;Belchior et al 2013). Non-targeted mechanisms comprise detrimental as well as protective bystander effects, genomic instability, adaptive response, induction of apoptosis and repopulation by cell killing (Truta-Popa et al 2011b).…”

Simulation and Sensitivity Analysis on the Parameter of Non-Targeted Irradiation Effects Model

“…As shown in Figure 5, survival of non-targeted cells decreases over the time. The survival cells also act independently in each dose because the DSBs formation in non-targeted cells are not dependent on dose [32]. At higher doses, the amount of bystander factors released by the irradiated cells almost saturated to the highest level that could be produced.…”