Abstract
Ionizing radiation (IR) in cancer radiotherapy can induce damage to neighboring cells via non-targeted effects by irradiated cells. These so-called bystander effects remain an area of interest as it may provide enhanced efficacy in killing carcinomas with minimal radiation. It is well known that reactive oxygen species (ROS) are ubiquitous among most biological activities. However, the role of ROS in bystander effects has not been thoroughly elucidated. We hypothesized that gradient irradiation (GI) has enhanced therapeutic effects via the ROS-mediated bystander pathways as compared to uniform irradiation (UI). We evaluated ROS generation, viability, and apoptosis in breast cancer cells (MCF-7) exposed to UI (5 Gy) or GI (8–2 Gy) in radiation fields at 2, 24 and 48 h after IR. We found that extracellular ROS release induced by GI was higher than that by UI at both 24 h (p < 0.001) and 48 h (p < 0.001). More apoptosis and less viability were observed in GI when compared to UI at either 24 h or 48 h after irradiation. The mean effective doses (ED) of GI were ~130% (24 h) and ~48% (48 h) higher than that of UI, respectively. Our results suggest that GI is superior to UI regarding redox mechanisms, ED, and toxic dosage to surrounding tissues.
Highlights
Previous research has shown that ionizing radiation (IR) can induce cells to emit signals that affect neighboring cells, termed non-targeted effects (NTE) [1, 2]
By comparing the uniform irradiation (UI) and gradient irradiation (GI) groups, we found that GI stimulated more reactive oxygen species (ROS) release as compared to UI at both 24 h (p < 0.001) and 48 h (p < 0.001), indicating a stronger redox-mediated bystander signal in the medium under GI
Our study suggests that GI is superior to UI in both redox advantage and toxic dosage to surrounding tissues
Summary
Previous research has shown that ionizing radiation (IR) can induce cells to emit signals that affect neighboring cells, termed non-targeted effects (NTE) [1, 2]. These studies show that tissues or organs respond collectively to IR dose damages which include both direct effects and NTE. One significant class of NTE, the bystander effects, is typically observed in less- or unirradiated cell. Cells that are exposed to bystander signals experience adverse effects including cell destruction, DNA damage, and gene mutation [4]. Despite some promising investigations on the radiation bystander effects, gaps still exist in the understanding of the quantitative aspects and its impact on radiobiological models
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