Reactive oxygen species formation and bystander effects in gradient irradiation on human breast cancer cells

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.

Central Nervous System Injury – A Newly Observed Bystander Effect of Radiation

“…The signaling pathways that might mediate the brain bystander effects of radiation in breast cancer patients remain unknown, but there is increasing evidence implicating ROS. Zhang et al report that the administration of ionizing radiation to breast cancer cells results in an increased production of the ROS O 2 – in both directly irradiated and neighboring cells [ 32 ]. These findings align with previous work demonstrating that unirradiated bystander cells demonstrate significant oxidative stress when co-cultured with irradiated cells [ 33 ].…”

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

“…Thus, ionizing radiation are waves or particles carrying enough energy to free electrons from atoms or molecules that in turn do generate reactive oxygen species (ROS). The latter are the main drivers of radiotherapy‐induced cellular damage …”

A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays

“…˙H, ˙e − aq and ˙O 2 − ). These reactive species damage biological molecules and contribute around 60% of the biological damage due to X-ray radiotherapy (Saenko et al 2013;Zhang et al 2016;Jayakumar et al 2014;reviewed in Baskar et al 2014). Although each clinical X-ray irradiation session only lasts for a few minutes, the radical-mediated damage can induce prolonged metabolic oxidative stress that continues to damage cells long after irradiation (Azzam et al 2012).…”