Initialising ...

Initialising ...

Initialising ...

Initialising ...

Initialising ...

Initialising ...

Initialising ...

Ouchi, Noriyuki

Evolution of Ionizing Radiation Research, p.41 - 62, 2015/09

Quantitative approach in radiation biology based on the clonogenic method and obtained cell survival curves as a dose-response relationship, are introduced. Generally, cell survival curves seem to have a universality on its function, i.e. functional form of survival curve seems to be unchanged under various conditions including different species. Various factors affecting the radiosensitivity have been introduced to find macroscopic nature of living organisms. Many mathematical models describing cell survival curves have been presented, however, functional form of cell survival curves derived from, based on biological mechanism does not yet exist. Finally, the possibility that the structural change of chromosome affects the repair process is discussed.

Sakashita, Tetsuya; Hamada, Nobuyuki*; Kawaguchi, Isao*; Ouchi, Noriyuki; Hara, Takamitsu*; Kobayashi, Yasuhiko; Saito, Kimiaki

PLOS ONE (Internet), 8(7), p.e70291_1 - e70291_10, 2013/07

Times Cited Count：7 Percentile：39.02(Multidisciplinary Sciences)Clonogenicity gives important information about the cellular reproductive potential following ionizing irradiation. We firstly plotted the experimentally determined colony size distribution of abortive colonies in irradiated normal human fibroblasts, and found the linear relationship on the log-log plot. By applying the simple model of branching processes to the linear relationship, we found the persistent reproductive cell death (RCD) over several generations following irradiation. To verify the estimated probability of RCD, abortive colony size distribution (15 cells/colony) and the surviving fraction were simulated by the Monte Carlo computational approach. Radiation-induced RCD (i.e. excess probability) lasted over 16 generations and mainly consisted of two components in the early and late phases. We found that short-term RCD is critical to the abortive colony size distribution, and long-lasting RDC is important for the dose response of the surviving fraction.

Ouchi, Noriyuki

Nihon Suri Seibutsu Gakkai Nyusu Reta, (68), p.5 - 8, 2012/09

Due to the Fukushima Dai-ichi Nuclear disaster in 2011, large amounts of radioactive has been released into the environment. As a results, studies of radiation health effects captured the strong attention, in general. Here, history of radiation health effects and biological effects are outlined, from initial radiobiological research to the dawn of molecular biological study, and some mathematical models are introduced.

Ouchi, Noriyuki

Current Topics in Ionizing Radiation Research, p.269 - 296, 2012/03

In general, we know that carcinogenesis by low dose radiation will start from DNA damage by ionizing radiation. Then, these very small effects will appear on a cellular scale by accumulation of various intracellular biological responses with spending long time and finally grow to the tumor with clonal expansion of cancer cell. In this review, we mainly focus on cellular level phenomena, i.e., process of the cell carcinogenesis and tumorigenesis. The contents will be as follows; (1) problem overview, (2) review of the biological radiation effects problem, (3) introduction of computational approach of the problem, (4) modeling radiation effects of cellular level, (5) simulation results and analysis (Growth-Curve analysis), (6) Conclusion and remarks.

Sakashita, Tetsuya; Suzuki, Michiyo; Ouchi, Noriyuki; Ban, Nobuhiko*

Hoshasen Seibutsu Kenkyu, 45(4), p.379 - 395, 2010/12

Recently, systems radiation biology (SRB) has been studied and developed in Europe and USA. Also, Japanese researchers in radiation biology are interested in this research field, gradually. In this review, four scientists shortly review SRB in each stand points.

Ouchi, Noriyuki

Radiation Protection Dosimetry, 143(2-4), p.365 - 369, 2010/12

Times Cited Count：1 Percentile：11.72(Environmental Sciences)Recent years, risk assessments of radiation induced cancer are getting worth for the public health view points. In general, we know that carcinogenesis by low dose radiation will start from DNA damage by ionizing radiation. After the long time period, these very small effects will appear on a cellular scale by accumulation of various intracellular biological responses and finally grow to the tumor with clonal expansion of cancer cell. Thus, the biological radiation effects are phenomena with a very wide scale from DNA damage to the tumor, so the risk estimation of low dose radiation is difficult to study by the experiments. To overcome these difficult situations at low dose radiation effects problem, it is good to study process of carcinogenesis using biologically based mathematical model. In this presentation, we will introduce our cellular scale mathematical model of tumorigenesis and show some results of statistical calculations about tumor growth curve.

Ouchi, Noriyuki

Data Science Journal (Internet), 6(Suppl.), p.S278 - S284, 2007/05

Biological effects of low-dose radiation are studied by computational methods. Assessing the risks of low-dose radiation, i.e. radiation induced cancer, is getting worth for the study of public health due to many types of exposures, medical exposures, and for the radiation protection view points. Here we introduce our on going study of describing low-dose radiation effects. Computer modeling and simulation are quite effective to clarify the mechanism of radiation effects since a phenomenon taking place in a small region in a very short time can be observed which is difficult to examine by experimental approaches. We will show our researches concerning the 3 stages of the radiation effects from atomic level to cellular level, (1) Simulation of DNA strand breaks by ionizing radiation, (2) Molecular dynamical study of the DNA lesion repair, (3) modeling and simulation of the cellular level tumorigenesis.

Ouchi, Noriyuki

Hoken Butsuri, 40(2), p.166 - 169, 2005/06

Development of the new mathematical model of the carcinogenesis in a low dose in mind is reported. The new model which describes from cell canceration to the tumorigenesis in consideration of the physical dynamics of a cell level was built. In a cell group level, it has both intra-cellular dynamics, such as mutation, cell division, and cell death, and physical dynamics such as, adhesion between cells, modification, and movement, and a model can investigate with time that tumor is formed.

Ouchi, Noriyuki; Glazier, J. A.*; Rieu, J.-P*; Upadhyaya, A.*; Sawada, Yasuji*

Physica A, 329(3-4), p.451 - 458, 2003/11

Times Cited Count：77 Percentile：91.08(Physics, Multidisciplinary)Because the extended large-Q Potts model captures effectively the global features of tissue rearrangement experiments, including cell sorting and tissue engulfment, it has become a common technique for cell level simulation of tissues. It agrees qualitatively with experiments. However, standard simulations using positive surface energies fail to describe correctly the dynamics of single cells moving within an aggregate. In particular, the hierarchy of diffusion constants is reversed compared to experiments. The standard model also suffers from numerical instabilities. In this letter, we show how to modify the Hamiltonian using negative surface energies and a spin flip energy threshold to improve the correspondence to experiments. We also investigate diffusion constant dependence on model parameters.

Ouchi, Noriyuki

no journal, ,

Recent years, our understandings about the contribution of physical stimulation(cell adhesion or cell shape, etc.) to the DNA synthesis or apoptosisin the process of cell carcinogenesis have advanced, and the importance of the research to clarify these factors to the carcinogenesis is getting worth more and more. Here, we are going to introduce the mathematical model of tumor growth based on the morphological study.

Saito, Kimiaki; Watanabe, Ritsuko; Higuchi, Mariko; Ouchi, Noriyuki; Akamatsu, Ken; Kinase, Sakae

no journal, ,

no abstracts in English

Ouchi, Noriyuki

no journal, ,

Cancer is a complex process crossing over several spatial and temporal scales, from the scale of DNA damages (10m) to the scale of tumor (10m). Modern mathematical model study of cancer started in the same time of discovery of DNA double helix structure. Nowadays, biological and molecular biological new findings, e.g. knowledge of upstream mechanism of mutation dynamics, cell microenvironment study, connection between cell fate and physical properties of cell, to name few, make mathematical model study difficult because we cannot use simple cell growth function. Here we introduce our individual based cell model with spatial structure and its simulation results about calculations of some statistical quantities.

Ouchi, Noriyuki

no journal, ,

Radiation dose, frequency of DNA strand breaks and frequency of chromosomal aberrations are commonly used for the measure of radiation effects. As we know, dose, DNA strand breaks and chromosomal aberrations are successive events, there are no common understandings for these relations. We are modeling chromosome using a kind of "toy-model", and extensively studied many dynamical features. Here, we will report on the physical properties of dynamics of chromosome, for example elastic movement, arising from computer simulation of our mathematical model.

Ouchi, Noriyuki

no journal, ,

Cancer, in a broad sense, is the leading cause of death for both men and women in Japan today; about 30% of people have died of cancer. It would be considered that half of the people will suffer from cancer in their lifetime. The process of carcinogenesis is considered as follows: (1) transformation of normal cell to cancer cell by acquiring mutations, (2) proliferation of cancer cells via clonal expansion, i.e. tumorigenesis, (3) tumor acquire malignancy by malignant transformation. As a mathematical expression of tumor growth process, initiation, promotion and progression (IPP) concept is used for modelling carcinogenesis. Ionizing radiation is thought to be one of the sources of IPP. In this presentation, cellular based mathematical model of tumorigenesis is shown and its dynamical aspects, especially based on morphological viewpoint are introduced.

Ouchi, Noriyuki; Pinak, M.

no journal, ,

As one of the measures of radiation effects, dose vs. frequency of DNA strand breaks (at the cellular level) or, frequency of chromosomal aberrations (at the individual level) are commonly used. As we know, dose, DNA strand breaks and chromosomal aberrations are successive events, there are no common understandings for these relations. We have investigated many types of chromosomal dynamics using mathematically modeled whole human chromosome 17. Here, we will report on the relationship between physical properties of dynamics of chromosomal broken ends and concentration speed of typical repair enzymes.

Ouchi, Noriyuki

no journal, ,

To consider biological effects of radiation based on the view point of radiation risk estimation, studying the DNA damage/cellular damage accumulation time scale is very important. Recent years, experimental data suggests that the major target of the radiation is cancer stem cell which is very localized cell within the tissue, elucidation of its dynamics have become an urgent matter. In this presentation, design process of mathematical model to study damage repair timescale (turn-over) is shown for the collaborating with the experiment.

Ouchi, Noriyuki

no journal, ,

Chromatin fiber is the container of DNA in Cell nucleus, its structure is changed drastically depending on the cell cycle, and make 10000 times condensed structure as known as chromosome at metaphase. Here we will show the simulation results of the mathematical model of chromosome/chromatin broken ends movement which will be produced by DSB, not only its dynamics but the dependency of cell cycle, and investigate the damage effectiveness on the whole system.

Sakashita, Tetsuya; Hamada, Nobuyuki*; Kawaguchi, Isao*; Ouchi, Noriyuki; Hara, Takamitsu*; Kobayashi, Yasuhiko; Saito, Kimiaki

no journal, ,

Clonogenicity gives important information about the cellular reproductive potential following ionizing irradiation. We firstly plotted the experimentally determined colony size distribution of abortive colonies in irradiated normal human fibroblasts, and found the linear relationship on the log-log plot. By applying the simple model of branching processes to the linear relationship, we found the persistent reproductive cell death (RCD) over several generations following irradiation. To verify the estimated probability of RCD, abortive colony size distribution (16 cells/colony) and the surviving fraction were simulated by the Monte Carlo computational approach. Radiation-induced RCD (i.e. excess probability) lasted over 16 generations and mainly consisted of two components in the early and late phases. These results suggest that short-term RCD is critical to the abortive colony size distribution, and long-lasting RDC is important for the dose response of the surviving fraction.