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.
authors.affiliation: Analytical Research Center for Experimental Sciences, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tokuyama
authors.affiliation: Heavy Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiobiological Sciences, 4-9-1 Anagawa, Inage Ward, Chiba 263-8555, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ide
authors.affiliation: Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba Ward, Sendai 980-8575, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.affiliation: Analytical Research Center for Experimental Sciences, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan terato@cc.saga-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Terato
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics*; D003412:Cricetulus; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000528:radiation effects*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D018499:Linear Energy Transfer; D008969:Molecular Sequence Data; D011829:Radiation Dosage
chemical_list: D004247:DNA
keywords: clustered DNA damage; heavy ion beam; high-LET radiation; oxidative base lesion; relative biological effectiveness (RBE)