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Journal Articles

Yield of single- and double-strand breaks and nucleobase lesions in fully hydrated plasmid DNA films irradiated with high-LET charged particles

Ushigome, Takeshi*; Shikazono, Naoya; Fujii, Kentaro; Watanabe, Ritsuko; Suzuki, Masao*; Tsuruoka, Chizuru*; Tauchi, Hiroshi*; Yokoya, Akinari

Radiation Research, 177(5), p.614 - 627, 2012/05

 Times Cited Count:14 Percentile:60.89(Biology)

The yield of DNA damage produced in fully hydrated plasmid DNA films has been investigated to determine the linear energy transfer (LET) dependence of damage induction. The yield of single strand breaks (SSBs) with increasing LET levels of He, C and Ne ions. On the other hand, the yields of prompt double strand breaks (DSBs) increased with increasing LET. SSBs were additionally induced by treatment with base excision repair proteins, glycosylases, indicating that base lesions are produced in the hydrated DNA. This result shows that nucleobase lesions are produced via both chemical reactions with diffusible water radicals and direct energy deposition onto DNA or the hydrated layer. The yield of SSBs or DSBs observed by enzymatic treatment notably decreased with increasing LET. These results indicated that higher LET ions preferentially produce a complex type of damage that might compromise the activities of the proteins used in this study.

Journal Articles

Analysis of cell-survival fractions for heavy-ion irradiations based on microdosimetric kinetic model implemented in the particle and heavy ion transport code system

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki*; Tsuruoka, Chizuru*; Suzuki, Masao*; Furusawa, Yoshiya*; Niita, Koji*

Radiation Protection Dosimetry, 143(2-4), p.491 - 496, 2011/02

 Times Cited Count:24 Percentile:88.73(Environmental Sciences)

We reanalyzed the survival fraction data, using the microdosimetric-kinetic (MK) model implemented in the PHITS code. It is found from the analysis that the MK model successfully accounts for the cell survival-fractions under a variety of irradiation conditions, using only y* parameter.

Oral presentation

Radiation-quality-dependence in bystander cellular effects on normal human cells induced by carbon-ion and X-ray microbeams

Suzuki, Masao*; Furusawa, Yoshiya*; Tsuruoka, Chizuru*; Kobayashi, Katsumi*; Usami, Noriko*; Maeda, Munetoshi*; Funayama, Tomoo; Sakashita, Tetsuya; Yokota, Yuichiro; Fukamoto, Kana; et al.

no journal, , 

no abstracts in English

Oral presentation

LET dependence of the yield of DNA strand breaks, base lesions and clustered damage sites induced in fully hydrated plasmid DNA films by ion particles

Yokoya, Akinari; Ushigome, Takeshi*; Tauchi, Hiroshi*; Suzuki, Masao*; Tsuruoka, Chizuru*; Noguchi, Miho; Fujii, Kentaro; Shikazono, Naoya; Watanabe, Ritsuko

no journal, , 

In order to clarify the characteristics of DNA damage induced by high LET radiation, the yields of strand breaks and base lesions induced in closed-circular plasmid DNA (pUC18) were measured after exposing to various kinds of radiation (He, Ne and C ions; 2 to 900 keV/$$mu$$m). Base excision repair enzymes were used to detect oxidative base lesions. The obtained results show that (1) the yield of prompt SSBs does not depend significantly on the LET, (2) whereas the yield of DSBs increases with increasing LET, (3) The yields of isolated nucleobase lesions detected by enzymes decrease drastically with increasing LET and (4) C and Ne ions induce less base lesions than He ions when compared in the same LET region. These results indicate that the yield of cluster of nucleobase lesions, which are less readily processed by the base excision repair proteins, depends not only LET but also ion species irradiated.

Oral presentation

Consideration on the LET dependence of DNA double strand breaks from the microdosimetric viewpoint

Watanabe, Ritsuko; Hirayama, Ryoichi*; Yokoya, Akinari; Terato, Hiroaki*; Tsuruoka, Chizuru*; Eguchi, Kiyomi*; Furusawa, Yoshiya*; Kobayashi, Katsumi*

no journal, , 

DNA double strand breaks (DSB) is thought to be the most critical damage for cell death. However, a considerable discrepancy is often observed between LET dependence of the frequency of cell death and that of the DSB yield. Also, several studies on the DSB yields as a function of LET have reported different tendency in the DSB-LET relationships. To obtain insight of the relationship between DSB and cell death, it is necessary to clarify the actual LET dependence of DSB. We have been discussing about the reason why the difference of the results depending on the groups. Here we will report on the results of our discussion. In particular, some points on the experimental detection system of DSB and the problems in calculation of absorbed dose (Gy) for particle beams will be discussed.

Oral presentation

Cell-type and ion-species dependences of the biological doses for charged-particle therapy

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki*; Tsuruoka, Chizuru*; Suzuki, Masao*; Furusawa, Yoshiya*; Niita, Koji*

no journal, , 

It is found from the calculation that the biological doses vary with the cell type by approximately 8 percents, but their depth distributions were almost independent of the cell type.

Oral presentation

Analysis of survival curves related to the spatial distribution and reparability of DNA damage

Watanabe, Ritsuko; Yokoya, Akinari; Suzuki, Masao*; Tsuruoka, Chizuru*; Hirayama, Ryoichi*; Furusawa, Yoshiya*

no journal, , 

In general, survival curves of mammalian cells can be fit by linear-quadratic model. However, it is still open question that what is the lethal damage and what kind of condition can be related to the linear and quadratic terms of the lethal damage. The purpose of this study is to elucidate and modeling the relationship between initial DNA damage and cell lethality. Here, the yield of lethal damage is estimated from experimentally obtained survival curves using linear-quadratic model. The estimated yields are compared with the simulated DNA spectrum and the spatial distribution such as the distance between damages in cell nucleus. From the comparison, the condition of initial damage related to the cell lethality is examined. In particular, LET and cell cycle dependent of survival curves are discussed relating to the initial DNA damage pattern and repair pathways, respectively.

Oral presentation

Direct action is the key to understand the high biological effects caused by particle beams

Hirayama, Ryoichi*; Matsumoto, Yoshitaka*; Uzawa, Akiko*; Takase, Nobuhiro*; Tsuruoka, Chizuru*; Wada, Mami*; Noguchi, Miho; Kase, Yuki*; Matsufuji, Naruhiro*; Ito, Atsushi*; et al.

no journal, , 

The contribution of indirect action mediated by OH radicals in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses indirect action of radiation without affecting direct action. Exponentially growing Chinese hamster ovary cells under oxic and hypoxic conditions were exposed to X-rays and iron ions having a dose-averaged LET at 200 keV/micrometer in the presence or absence of DMSO, and the cell survival was determined using the colony formation assay. The contributions of indirect action of 76% and 50% were found for X-rays under oxic and hypoxic conditions, respectively. In contrast, the contributions of indirect action for iron ions were estimated to be 42% and 32%. The RBE values were 2.8 for oxic and 5.3 for hypoxic, and the OER values were 2.8 for X-rays and 1.5 for iron ions. When the RBE and OER were estimated separately for direct action (RBE(D) and OER(D)) and indirect action (RBE(I) and OER(I)); the RBE(D) was larger than RBE(I) under both normal and low oxygen concentrations. The OER(D) values for both X-rays and iron ions were lower than that for OER(I). Thus, direct action of radiation gives a remarkably higher RBE and lower OER for cell killing than indirect action. It is possible that particle beams may be highly effective in treating cancer if the particle therapy can only use the portion of direct action out of total radiation actions; this would be exemplified by the usage of radioactive 9C-ion beams and boron neutron capture.

Oral presentation

Dependence of the yields of AP sites and AP clusters produced in pUC18 plasmid DNA on scavenging capacity and radiation quality and LET

Shiina, Takuya; Sugaya, Yuki; Shiraishi, Iyo; Watanabe, Ritsuko; Yokoya, Akinari; Tsuruoka, Chizuru*; Suzuki, Masao*

no journal, , 

There has been very little knowledge of AP sites and AP clusters induced by heavy ion beam irradiation. In order to clarify the relation between track structure of C ions (290MeV/nucleon, LET 13, 60keV/$$mu$$m) or X-rays and the induction processes of an AP or AP clusters, we measure the yield of AP sites visualized by the treatment of irradiated pUC18 plasmid DNA with the AP endoclease (Nfo), which converts an AP site to detectable single strand break. Several scavenging capacities of the samples are tested to estimate the effect of indirect action of diffusible OH radicals in the induction of AP site. These experimental data will be discussed with theoretical radiation track structure in the respect of repair susceptibility of the AP cluster.

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