Neighbor effect: penumbra-dose exposed neighbor cells contribute to the enhanced survival of high-dose targeted cells

Abstract

Purpose: In the last decade, new types of ‘bystander effect’ have been suggested by multiple research groups and have been challenged by others. In this study, we explored a new type of bystander effect, which has been defined in previous studies as the enhancement of the survival of high-dose targeted cells due to the penumbra-dose exposed neighbor cells. Intensity-modulated radiation therapy, which is the most widely used treatment modality, generates local regions of gradient doses between targeted and shielded cells throughout the treatment volume; therefore, we were urged to ascertain whether the new type of effect is real and to suggest a revised treatment planning.

Materials and methods: Cellular responses under non-uniform beam fields were observed in rat gliosarcoma cells, rat diencephalon cells, and mouse endothelial cells. The cells were irradiated with 200 kVp X-rays in two types: (1) all the cells in the flask were exposed to the X-ray beam (whole-beam exposure) and (2) half of the cells in the flask were exposed to the beam while the other half, or neighbor cells, were shielded from the beam (half-beam exposure). Target cells were exposed to 1, 2, 4, 6, 8, and 10 Gy, and the penumbra dose was approximately 10%–20% of the target dose.

Results: Target cells survived high-dose (> 6 Gy) radiation exposures better under half-beam exposure with the low penumbra-dose exposed neighbor cells around than under whole-beam exposure. The survival of the targeted cells from half-beam exposure was reduced when the radiation self-conditioned medium was replaced with a fresh one immediately after irradiation. Survival was further reduced when the targeted cells were harvested immediately after irradiation and incubated in new dishes with fresh culture media until the colony was counted.

Conclusion: We have collected data of good statistics by several post-irradiation treatments of targeted cells to ascertain that the new type of bystander effect is real. The low penumbra-dose exposed neighbor cells benefited the survival of the high-dose targeted cells.

Keywords:

• Modulated beam exposure
• dose-gradient boundary
• radiation-induced bystander effect
• neighbor effect

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This work was supported by Basic Research Program through the National Research Foundation of Korea funded by Korea Ministry of Science, ICT and Future Planning [No. 2013R1A1A3012355].

Notes on contributors

Mr. Min-Ho Lee is a Ph.D. candidate in Department of Nuclear Engineering at Seoul National University. He received his Bachelor?s degree in Department of Nuclear Engineering from Seoul National University in 2010. His research interests include radiation biology, especially low-dose effect.

Dr. Ki-Man Lee received his Ph.D. degree in Department of Nuclear Engineering from Seoul National University. He is currently a senior researcher in the Neutron Utilization Research Division at the Korea Atomic Energy Research Institute. His research focus is on the radiation dosimetry, radiation spectrometry and neutron activation analysis.

Professor Eun-Hee Kim is a nuclear engineer with a specialty in radiation protection. She explores new approaches for better understanding the biological effect of radiation. Her research team has built an electron microbeam irradiation system, a hard X-ray irradiation facility, and an alpha irradiator for its own research purposes.