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Journal Articles

Oxygen enhancement ratios of cancer cells after exposure to intensity modulated X-ray fields; DNA damage and cell survival

Matsuya, Yusuke; McMahon, S. J.*; Butterworth, K. T.*; Naijo, Shingo*; Nara, Isshi*; Yachi, Yoshie*; Saga, Ryo*; Ishikawa, Masayori*; Sato, Tatsuhiko; Date, Hiroyuki*; et al.

Physics in Medicine & Biology, 66(7), p.075014_1 - 075014_11, 2021/04

 Times Cited Count:0 Percentile:0.01(Engineering, Biomedical)

Hypoxic cancer cells within solid tumours show radio-resistance, leading to malignant progression in fractionated radiotherapy. When prescribing dose to tumours under heterogeneous oxygen pressure with intensity-modulated radiation fields, intercellular signalling could have an impact on radiosensitivity between in-field and out-of-field cells. However, the impact of hypoxia on radio-sensitivity under modulated radiation intensity remains uncertain. In this study, we investigate the impact of hypoxia on in-field and out-of-field radio-sensitivities using two types of cancer cells. These in vitro measurements indicate that hypoxia apparently impacts out-of-field cells, although the OER values in out-of-field cells were smaller compared to those for in-field and uniformly irradiated cells. These decreased radio-sensitivities of out-of-field cells were shown as a consistent tendency for both DSB and cell death endpoints, suggesting that radiation-induced intercellular communication is of importance in treatment planning with intensity-modulated radiotherapy.

Journal Articles

Intensity modulated radiation fields induce protective effects and reduce importance of dose-rate effects

Matsuya, Yusuke; McMahon, S. J.*; Ghita, M.*; Yoshii, Yuji*; Sato, Tatsuhiko; Date, Hiroyuki*; Prise, K. M.*

Scientific Reports (Internet), 9(1), p.9483_1 - 9483_12, 2019/07

 Times Cited Count:6 Percentile:65.54(Multidisciplinary Sciences)

In radiotherapy, intensity modulated radiation fields and complex dose-delivery are used to prescribe doses to tumors. Here, we analyzed the impact of modulated field on radio-sensitivity and cell recovery during irradiation time. The dose was delivered to either 50% of the area of the flask containing cells (half-field) or 100% of the flask (uniform-field). We also modelled cell-killing considering dose-rate effects and intercellular signals. It is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure even with the same dose; (ii) the importance of sub-lethal damage repair in normal human skin fibroblast cells under the half-field is reduced; (iii) the increase of cell survival under half-field is predominantly attributed to not rescue effects (increased repair) but protective effects (reduced initial DNA lesion yield). These findings provide new understanding of radio-sensitivity for hit and non-hit cells under non-uniform exposure.

Journal Articles

A New Standard DNA Damage (SDD) data format

Schuemann, J.*; McNamara, A. L.*; Warmenhoven, J. W.*; Henthorn, N. T.*; Kirkby, K.*; Merchant, M. J.*; Ingram, S.*; Paganetti, H.*; Held, K. D.*; Ramos-Mendez, J.*; et al.

Radiation Research, 191(1), p.76 - 93, 2019/01

 Times Cited Count:34 Percentile:97.99(Biology)

We propose a new Standard DNA Damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modelling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

JAEA Reports

Information basis for developing comprehensive waste management system; US-Japan Joint Nuclear Energy Action Plan Waste Management Working Group Phase I report (Joint research)

Yui, Mikazu; Ishikawa, Hirohisa; Watanabe, Atsuo*; Yoshino, Kyoji*; Umeki, Hiroyuki; Hioki, Kazumasa; Naito, Morimasa; Seo, Toshihiro; Makino, Hitoshi; Oda, Chie; et al.

JAEA-Research 2010-015, 106 Pages, 2010/05


This report summarizes the activity of Phase I of Waste Management Working Group of the United States - Japan Joint Nuclear Energy Action Plan started in 2007. The working group focused on consolidation of the existing technical basis between the U.S. and Japan and the joint development of a plan for future collaborative activities. Firstly, the political/regulatory frameworks related to nuclear fuel cycles in both countries were reviewed. The various advanced fuel cycle scenarios in both countries were surveyed and summarized. Secondly, the waste management/disposal system optimization was discussed. Repository system concepts for the various classifications of nuclear waste were reviewed and summarized, then disposal system optimization processes and techniques were reviewed, and factors to consider in future repository design optimization activities were also discussed. Finally the potential collaboration areas and activities related to the optimization problem were extracted.

Oral presentation

An Integrated theoretical model for estimating cell death based on the DNA damage response

Matsuya, Yusuke; McMahon, S. J.*; Sato, Tatsuhiko; Butterworth, K. T.*; Saga, Ryo*; Date, Hiroyuki*; Prise, K. M.*

no journal, , 

Ionizing radiation has the potential to induce damage to DNA and subsequent late biological effects such as cell death. Amongst the types of DNA lesions, DNA double-strand breaks (DSBs) have been known as the principal damage form leading to cell death with a certain probability. To date, early DSB induction and the repair dynamics have been experimentally investigated, yet the optimum approach to directly evaluate the relationship between DSBs and cell death remain unclear. To solve this problem, we have developed a theoretical cell-killing model, the integrated microdosimetric-kinetic (IMK) model, which considers the responses of sub-lethal damage (corresponding to DSB) after irradiation and several biological factors, such as cell-cycle phase, oxygen pressure and intercellular communication. Using the IMK model, we have successfully reproduced experimental DSBs and survival data for various irradiation conditions and cell conditions. In this study, we introduce an overview of the IMK model. In particular, focusing on early DSBs yield and the repair kinetics, we present the latest estimation results for interpreting the cellular mechanisms of intercellular communication and oxygen effects. In the future, by developing an integrated package enabling to estimate cellular responses in the combination of the PHITS code and the IMK model, it will be expected to clarify the relationship between initial DNA damage and late biological effects, such as cell death and mutation.

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