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Recovery from sublethal damage and potentially lethal damage

Proton beam irradiation vs. X‑ray irradiation

Erholung von subletalen und potenziell letalen Schäden

Protonenbestrahlung vs. Röntgenbestrahlung

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Abstract

Purpose

In order to clarify the biological response of tumor cells to proton beam irradiation, sublethal damage recovery (SLDR) and potentially lethal damage recovery (PLDR) induced after proton beam irradiation at the center of a 10 cm spread-out Bragg peak (SOBP) were compared with those seen after X‑ray irradiation.

Methods

Cell survival was determined by a colony assay using EMT6 and human salivary gland tumor (HSG) cells. First, two doses of 4 Gy/GyE (Gray equivalents, GyE) were given at an interfraction interval of 0–6 h. Second, five fractions of 1.6 Gy/GyE were administered at interfraction intervals of 0–5 min. Third, a delayed-plating assay involving cells in plateau-phase cultures was conducted. The cells were plated in plastic dishes immediately or 2–24 h after being irradiated with 8 Gy/GyE of X‑rays or proton beams. Furthermore, we investigated the degree of protection from the effects of X‑rays or proton beams afforded by the radical scavenger dimethyl sulfoxide to estimate the contribution of the indirect effect of radiation.

Results

In both the first and second experiments, SLDR was more suppressed after proton beam irradiation than after X‑ray irradiation. In the third experiment, there was no difference in PLDR between the proton beam and X‑ray irradiation conditions. The degree of protection tended to be higher after X‑ray irradiation than after proton beam irradiation.

Conclusion

Compared with that seen after X‑ray irradiation, SLDR might take place to a lesser extent after proton beam irradiation at the center of a 10 cm SOBP, while the extent of PLDR does not differ significantly between these two conditions.

Zusammenfassung

Zielsetzung

Zur Klärung der biologischen Reaktion von Tumorzellen auf eine Protonenbestrahlung wurden die Erholung von subletalen Schäden (SLDR; „sublethal damage recovery“) und die von potenziell letalen Schäden (PLDR; „potentially lethal damage recovery“), induziert nach Protonenbestrahlung in der Mitte eines 10-cm-Spread-out-Bragg-Peak (SOBP), untersucht und mit der nach Röntgenbestrahlung verglichen.

Methoden

Das Zellüberleben wurde in einem Kolonie-Assay mit EMT6- und HSG-Zellen („human salivary gland tumor“) bestimmt. Erstens wurden zwei Dosen mit 4 Gy/GyE (Äquivalentdosis) mit einem interfraktionellen Intervall von 0–6 h appliziert. Zweitens wurden fünf Fraktionen zu je 1,6 Gy/GyE in interfraktionellen Intervallen von 0–5 min verabreicht. Drittens wurde ein Test mit einer Reparaturzeit („delayed plating assay“) an Kulturen in der stationären Phase durchgeführt. Die Zellen wurden entweder sofort oder 2–24 h nach Bestrahlung mit 8 Gy/GyE-Röntgen- oder Protonenstrahlen in Kunststoffschalen ausplattiert. Des Weiteren untersuchten wir die Schutzwirkung des Radikalfängers Dimethylsulfoxid (DMSO) hinsichtlich der Schäden durch Röntgen- bzw. Protonenstrahlung, um den Anteil der indirekten Auswirkungen einer Bestrahlung abzuschätzen.

Ergebnisse

Im ersten und zweiten Experiment war die SLDR nach Protonenbestrahlung stärker supprimiert als nach Röntgenbestrahlung. Im dritten Experiment bestand bei keinem Zelltyp ein Unterschied in der PLDR zwischen Protonen- und Röntgenstrahlenexposition. Die DMSO-Schutzwirkung war nach Röntgenbestrahlung tendenziell höher als nach Protonenbestrahlung.

Schlussfolgerung

Verglichen mit der SLDR nach Röntgenbestrahlung findet nach Protonenbestrahlung in der Mitte des 10-cm-SOBP möglicherweise ein geringeres Maß an SLDR statt, während bei der PLDR kein signifikanter Unterschied zwischen beiden Strahlenarten besteht.

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Acknowledgements

The authors wish to thank Toshiyuki Toshito, PhD, Hideto Kinou, and Masaki Katsurada, for their valuable help with this research.

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Authors and Affiliations

  1. Department of Radiation Oncology, Nagoya Proton Therapy Center, 1-1-1 Hirate-cho, Kita-ku, 462-8508, Nagoya, Japan

    Shingo Hashimoto MD, PhD, Hiromitsu Iwata MD, PhD, Hiroyuki Ogino MD, PhD & Jun-etsu Mizoe MD, PhD

  2. Department of Radiation Oncology, Nagoya City West Medical Center, 1-1-1 Hirate-cho, Kita-ku, 462-8508, Nagoya, Japan

    Shingo Hashimoto MD, PhD

  3. Department of Radiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, 467-8601, Nagoya, Japan

    Shingo Hashimoto MD, PhD, Chikao Sugie MD, PhD & Yuta Shibamoto MD, PhD

  4. Department of Proton Therapy Physics, Nagoya Proton Therapy Center, 1-1-1 Hirate-cho, Kita-ku, 462-8508, Nagoya, Japan

    Chihiro Omachi PhD

  5. Faculty of Radiological Technology School of Health Sciences, Fujita Health University, 1–98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Aichi, Japan

    Keisuke Yasui PhD

  6. Osaka Heavy Ion Center, 3-3-8 Otemae, Chou-ku, 540-0008, Osaka, Japan

    Jun-etsu Mizoe MD, PhD

Authors
  1. Shingo Hashimoto MD, PhD
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  2. Chikao Sugie MD, PhD
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  3. Hiromitsu Iwata MD, PhD
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  4. Hiroyuki Ogino MD, PhD
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  5. Chihiro Omachi PhD
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  6. Keisuke Yasui PhD
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  7. Jun-etsu Mizoe MD, PhD
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  8. Yuta Shibamoto MD, PhD
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Corresponding author

Correspondence to Shingo Hashimoto MD, PhD.

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Conflict of interest

C. Sugie received JSPS KAKENHI grant numbers 25870609, 16K10400. H. Iwata received JSPS KAKENHI grant numbers 15H05675. S. Hashimoto, H. Ogino, C. Omachi, K. Yasui, J.-e. Mizoe and Y. Shibamoto declare that they have no competing interests.

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Hashimoto, S., Sugie, C., Iwata, H. et al. Recovery from sublethal damage and potentially lethal damage. Strahlenther Onkol 194, 343–351 (2018). https://doi.org/10.1007/s00066-017-1223-9

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