Distinct modes of death in human neural stem and glioblastoma cells irradiated with carbon-ion radiation and gamma-rays

Abstract

Purpose: Accumulated damage in neural stem cells (NSCs) during brain tumor radiotherapy causes cognitive dysfunction to the patients. Carbon-ion radiotherapy can reduce undesired irradiation of normal tissues more efficiently than conventional photon radiotherapy. This study elucidates the responses of NSCs to carbon-ion radiation.

Methods: Human NSCs and glioblastoma A-172 cells were irradiated with carbon-ion radiation and γ-rays, which have different linear-energy-transfer (LET) values of 108 and 0.2 keV/μm, respectively. After irradiation, growth rates were measured, apoptotic cells were detected by flow cytometry, and DNA synthesizing cells were immunocytochemically visualized.

Results: Growth rates of NSCs and A-172 cells were decreased after irradiation. The percentages of apoptotic cells were remarkably increased in NSCs but not in A-172 cells. In contrast, the fractions of DNA synthesizing A-172 cells were decreased in a dose-dependent manner. These results indicate that apoptosis induction and DNA synthesis inhibition contribute to the growth inhibition of NSCs and glioblastoma cells, respectively. In addition, high-LET carbon ions induced more profound effects than low-LET γ-rays.

Conclusions: Apoptosis is an important clinical target to protect NSCs during brain tumor radiotherapy using carbon-ion radiation as well as conventional X-rays.

Keywords:

• Neural stem cells
• glioblastoma cells
• carbon-ion radiation
• linear energy transfer
• apoptosis

Acknowledgements

The authors thank the members of the project ‘Microbeam Radiation Biology’ in the QST-TARRI for their useful comments and help. The authors also thank the operators of the TIARA and Co60 irradiation facility in the QST-TARRI for their technical cooperation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was partly supported by JSPS KAKENHI Grant Number 16K00552 and 18H04991 to T. F.

Notes on contributors

Yuichiro Yokota

Yuichiro Yokota, PhD, is a Principal Researcher at Department of Radiation-Applied Biology Research, Takasaki Advanced Radiation Research Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology. His research field is radiation biology, and his interests are in the differences between radioresistant and radiosensitive organisms.

Yutaka Wada

Yutaka Wada, MMSc, was a Postgraduate Student in the Graduate School of Medicine of Gunma University and participated in this study as a student trainee in the project of Y.Y. and T.F.

Tomoo Funayama

Tomoo Funayama, PhD, is a Project Leader at Department of Radiation-Applied Biology Research, Takasaki Advanced Radiation Research Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology. His research field is radiation biology, and he has been focused on the biological application of heavy-ion microbeam.