Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation

Yuka Tokuyama, Yoshiya Furusawa, Hiroshi Ide, Akira Yasui, Hiroaki Terato

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance of clustered DNA damage in the biological effects of heavy ion beam radiation. In this study, we analyzed the yield of clustered base damage (comprising multiple base lesions) in cultured cells irradiated with various heavy ion beams, and investigated isolated base damage and the repair process in post-irradiation cultured cells. Chinese hamster ovary (CHO) cells were irradiated by carbon, silicon, argon and iron ion beams with LETs of 13, 55, 90 and 200 keV μm-1, respectively. Agarose gel electrophoresis of the cells with enzymatic treatments indicated that clustered base damage yields decreased as the LET increased. The aldehyde reactive probe procedure showed that isolated base damage yields in the irradiated cells followed the same pattern. To analyze the cellular base damage process, clustered DNA damage repair was investigated using DNA repair mutant cells. DNA double-strand breaks accumulated in CHO mutant cells lacking Xrcc1 after irradiation, and the cell viability decreased. On the other hand, mouse embryonic fibroblast (Mef) cells lacking both Nth1 and Ogg1 became more resistant than the wild type Mef. Thus, clustered base damage seems to be involved in the expression of heavy ion beam biological effects via the repair process.

Original languageEnglish
Pages (from-to)446-455
Number of pages10
JournalJournal of Radiation Research
Volume56
Issue number3
DOIs
Publication statusPublished - Dec 5 2014
Externally publishedYes

Fingerprint

Heavy Ions
DNA Damage
heavy ions
deoxyribonucleic acid
ion beams
damage
Linear Energy Transfer
irradiation
Cricetulus
Ionizing Radiation
DNA Repair
Ovary
Cultured Cells
Fibroblasts
ovaries
linear energy transfer (LET)
biological effects
Double-Stranded DNA Breaks
Agar Gel Electrophoresis
hamsters

Keywords

  • Clustered DNA damage
  • Heavy ion beam
  • High-LET radiation
  • Oxidative base lesion
  • Relative biological effectiveness (RBE)

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

Cite this

Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation. / Tokuyama, Yuka; Furusawa, Yoshiya; Ide, Hiroshi; Yasui, Akira; Terato, Hiroaki.

In: Journal of Radiation Research, Vol. 56, No. 3, 05.12.2014, p. 446-455.

Research output: Contribution to journalArticle

@article{01c76d2dbdc04e8e9c230a44cac8cf64,
title = "Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation",
abstract = "Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance of clustered DNA damage in the biological effects of heavy ion beam radiation. In this study, we analyzed the yield of clustered base damage (comprising multiple base lesions) in cultured cells irradiated with various heavy ion beams, and investigated isolated base damage and the repair process in post-irradiation cultured cells. Chinese hamster ovary (CHO) cells were irradiated by carbon, silicon, argon and iron ion beams with LETs of 13, 55, 90 and 200 keV μm-1, respectively. Agarose gel electrophoresis of the cells with enzymatic treatments indicated that clustered base damage yields decreased as the LET increased. The aldehyde reactive probe procedure showed that isolated base damage yields in the irradiated cells followed the same pattern. To analyze the cellular base damage process, clustered DNA damage repair was investigated using DNA repair mutant cells. DNA double-strand breaks accumulated in CHO mutant cells lacking Xrcc1 after irradiation, and the cell viability decreased. On the other hand, mouse embryonic fibroblast (Mef) cells lacking both Nth1 and Ogg1 became more resistant than the wild type Mef. Thus, clustered base damage seems to be involved in the expression of heavy ion beam biological effects via the repair process.",
keywords = "Clustered DNA damage, Heavy ion beam, High-LET radiation, Oxidative base lesion, Relative biological effectiveness (RBE)",
author = "Yuka Tokuyama and Yoshiya Furusawa and Hiroshi Ide and Akira Yasui and Hiroaki Terato",
year = "2014",
month = "12",
day = "5",
doi = "10.1093/jrr/rru122",
language = "English",
volume = "56",
pages = "446--455",
journal = "Journal of Radiation Research",
issn = "0449-3060",
publisher = "Japan Radiation Research Society",
number = "3",

}

TY - JOUR

T1 - Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation

AU - Tokuyama, Yuka

AU - Furusawa, Yoshiya

AU - Ide, Hiroshi

AU - Yasui, Akira

AU - Terato, Hiroaki

PY - 2014/12/5

Y1 - 2014/12/5

N2 - Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance of clustered DNA damage in the biological effects of heavy ion beam radiation. In this study, we analyzed the yield of clustered base damage (comprising multiple base lesions) in cultured cells irradiated with various heavy ion beams, and investigated isolated base damage and the repair process in post-irradiation cultured cells. Chinese hamster ovary (CHO) cells were irradiated by carbon, silicon, argon and iron ion beams with LETs of 13, 55, 90 and 200 keV μm-1, respectively. Agarose gel electrophoresis of the cells with enzymatic treatments indicated that clustered base damage yields decreased as the LET increased. The aldehyde reactive probe procedure showed that isolated base damage yields in the irradiated cells followed the same pattern. To analyze the cellular base damage process, clustered DNA damage repair was investigated using DNA repair mutant cells. DNA double-strand breaks accumulated in CHO mutant cells lacking Xrcc1 after irradiation, and the cell viability decreased. On the other hand, mouse embryonic fibroblast (Mef) cells lacking both Nth1 and Ogg1 became more resistant than the wild type Mef. Thus, clustered base damage seems to be involved in the expression of heavy ion beam biological effects via the repair process.

AB - Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance of clustered DNA damage in the biological effects of heavy ion beam radiation. In this study, we analyzed the yield of clustered base damage (comprising multiple base lesions) in cultured cells irradiated with various heavy ion beams, and investigated isolated base damage and the repair process in post-irradiation cultured cells. Chinese hamster ovary (CHO) cells were irradiated by carbon, silicon, argon and iron ion beams with LETs of 13, 55, 90 and 200 keV μm-1, respectively. Agarose gel electrophoresis of the cells with enzymatic treatments indicated that clustered base damage yields decreased as the LET increased. The aldehyde reactive probe procedure showed that isolated base damage yields in the irradiated cells followed the same pattern. To analyze the cellular base damage process, clustered DNA damage repair was investigated using DNA repair mutant cells. DNA double-strand breaks accumulated in CHO mutant cells lacking Xrcc1 after irradiation, and the cell viability decreased. On the other hand, mouse embryonic fibroblast (Mef) cells lacking both Nth1 and Ogg1 became more resistant than the wild type Mef. Thus, clustered base damage seems to be involved in the expression of heavy ion beam biological effects via the repair process.

KW - Clustered DNA damage

KW - Heavy ion beam

KW - High-LET radiation

KW - Oxidative base lesion

KW - Relative biological effectiveness (RBE)

UR - http://www.scopus.com/inward/record.url?scp=84929938447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929938447&partnerID=8YFLogxK

U2 - 10.1093/jrr/rru122

DO - 10.1093/jrr/rru122

M3 - Article

C2 - 25717060

AN - SCOPUS:84929938447

VL - 56

SP - 446

EP - 455

JO - Journal of Radiation Research

JF - Journal of Radiation Research

SN - 0449-3060

IS - 3

ER -