title: 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.
authors.affiliation: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA.|Urology Nevada/Northern Nevada Radiation Oncology, Reno, NV 89521, USA.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA.|Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Tingyang
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, NY 12866, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, The James Cancer Hospital, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Rong
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
authors.forename: Shin Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.|Department of Chemistry and Biochemistry, Molecular and Cellular Biology Program, Ohio University, Athens, OH 45701, USA.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wu
authors.affiliation: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA.|Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.|Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D024201:Bystander Effect / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D017382:Reactive Oxygen Species; D045304:Cytochromes c
keywords: MCF-7; breast cancer cells; bystander effects; gradient irradiation; reactive oxygen species