No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields

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...

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Main Authors: Hisanori Fukunaga, Kiichi Kaminaga, Eri Hirose, Ritsuko Watanabe, Noriko Usami, Kevin M. Prise, Akinari Yokoya
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/23/12785
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author Hisanori Fukunaga
Kiichi Kaminaga
Eri Hirose
Ritsuko Watanabe
Noriko Usami
Kevin M. Prise
Akinari Yokoya
author_facet Hisanori Fukunaga
Kiichi Kaminaga
Eri Hirose
Ritsuko Watanabe
Noriko Usami
Kevin M. Prise
Akinari Yokoya
author_sort Hisanori Fukunaga
collection DOAJ
description 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.
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spelling doaj.art-79af8e2f8f544416b6b3f55355b14cb42023-11-23T02:28:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231278510.3390/ijms222312785No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation FieldsHisanori Fukunaga0Kiichi Kaminaga1Eri Hirose2Ritsuko Watanabe3Noriko Usami4Kevin M. Prise5Akinari Yokoya6Center for Environmental and Health Sciences, Hokkaido University, N12 W7 Kita-ku, Sapporo 060-0812, JapanInstitute for Quantum Life Science, National Institutes for Quantum Science and Technology, 2-4 Shirakata, Tokai 319-1106, JapanGraduate School of Science and Engineering, Ibaraki University, 2-1-1 Bunkyo, Mito 310-8512, JapanInstitute for Quantum Life Science, National Institutes for Quantum Science and Technology, 2-4 Shirakata, Tokai 319-1106, JapanPhoton Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba 305-0801, JapanPatrick G Johnston Centre for Cancer Research, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UKInstitute for Quantum Life Science, National Institutes for Quantum Science and Technology, 2-4 Shirakata, Tokai 319-1106, JapanThe 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.https://www.mdpi.com/1422-0067/22/23/12785cell cyclefluorescent ubiquitination-based cell-cycle indicatorHeLa cellnon-targeted effectmicrobeamradiotherapy
spellingShingle Hisanori Fukunaga
Kiichi Kaminaga
Eri Hirose
Ritsuko Watanabe
Noriko Usami
Kevin M. Prise
Akinari Yokoya
No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields
International Journal of Molecular Sciences
cell cycle
fluorescent ubiquitination-based cell-cycle indicator
HeLa cell
non-targeted effect
microbeam
radiotherapy
title No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields
title_full No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields
title_fullStr No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields
title_full_unstemmed No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields
title_short No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields
title_sort no intercellular regulation of the cell cycle among human cervical carcinoma hela cells expressing fluorescent ubiquitination based cell cycle indicators in modulated radiation fields
topic cell cycle
fluorescent ubiquitination-based cell-cycle indicator
HeLa cell
non-targeted effect
microbeam
radiotherapy
url https://www.mdpi.com/1422-0067/22/23/12785
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