Research Papers:

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

Dongqing Zhang, Tingyang Zhou, Feng He, Yi Rong, Shin Hee Lee, Shiyong Wu and Li Zuo _

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Oncotarget. 2016; 7:41622-41636. https://doi.org/10.18632/oncotarget.9517

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Dongqing Zhang1,6,*, Tingyang Zhou1,5,*, Feng He3,*, Yi Rong2, Shin Hee Lee7, Shiyong Wu7,8, Li Zuo1,4,5

1Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA

2Department of Radiation Oncology, The James Cancer Hospital, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA

3Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, NY 12866, USA

4Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA

5Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA

6Urology Nevada/Northern Nevada Radiation Oncology, Reno, NV 89521, USA

7Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA

8Department of Chemistry and Biochemistry, Molecular and Cellular Biology Program, Ohio University, Athens, OH 45701, USA

*These authors are equally contributed to this work

Correspondence to:

Li Zuo, email: zuo.4@osu.edu

Keywords: bystander effects, reactive oxygen species, gradient irradiation, breast cancer cells, MCF-7

Received: August 19, 2015     Accepted: April 18, 2016     Published: May 20, 2016


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.

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