Abstract
The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa–FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 μm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell–cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa–FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics.
Highlights
Recent advances in radiotherapeutic technology have made it possible to efficiently focus the dose to the planned target volume (PTV); the approach to completely irradiate only tumor cells has not yet been established
Where irradiated areas and non-irradiated areas coexist, it is known that cells that do not directly receive radiation doses receive signals from neighboring irradiated cells and behave as though they have been exposed to modified radiation fields
From the point of view radiation biology, and clinical oncology, it is important to understand how the cell cycle is regulated in spatially modulated radiation fields
Summary
Recent advances in radiotherapeutic technology have made it possible to efficiently focus the dose to the planned target volume (PTV); the approach to completely irradiate only tumor cells has not yet been established. In this study, using intensity-modulated radiation fields and the FUCCI technique, we investigated the non-targeted effects of radiation on the cell cycle in HeLa cells. In the current study, the intercellular control of the cell cycle in HeLa cells, via soluble factors and cell–cell contacts, following exposure to modulated and micro-slit X-ray fields was not detected, which suggested that the unregulated cell growth was a malignant tumor. It may be that there is no synergy between chemotherapy with cell-cycle inhibitors and non-targeted effects associated with radiation therapy Modern radiotherapy techniques, such as intensity-modulated radiotherapy, imageguided radiotherapy, and tomotherapy, can conform precious dose distributions to target tumors, thereby reducing the adverse effects in normal surrounding tissues. We would prefer to use flow cytometry to examine the criminal changes in the cell cycle of irradiated and non-irradiated cells, for example, in cells without FUCCI or other cancer cells
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