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.