研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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A Beverage Containing Fermented Black Soybean Ameliorates Ferric Nitrilotriacetate-Induced Renal Oxidative Damage in Rats Open Access

Okazaki Yasumasa, Iqbal Mohammad, Kawakami Norito, Yamamoto Yorihiro, Toyokuni Shinya, Okada Shigeru

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 47 巻 ( 3 ) 頁： 198 - 207 2010年11月

Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. 査読有り国際誌

Nagai H, Toyokuni S

Archives of biochemistry and biophysics 502 巻 ( 1 ) 頁： 1 - 7 2010年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Archives of Biochemistry and Biophysics

Nano-sized durable fibrous materials such as carbon nanotubes have raised safety concerns similar to those raised by asbestos. However, the mechanism by which particulates with ultrafine structure cause inflammation and ultimately cancer (e.g. malignant mesothelioma and lung cancer) is largely unknown. This is partially because the particulates are not uniform and they vary in a plethora of factors. Such variances include length, diameter, surface area, density, shape, contaminant metals (including iron) and crystallinity. Each of these factors is involved in particulate toxicity both in vitro and in vivo. Thus, the elicited biological responses are incredibly complicated. Various kinds of fibers were evaluated with different cells, animals and methods. The aim of this review is to concisely summarize previous reports from the standpoint that activation of macrophages and mesothelial injury are the two major mechanisms of inflammation and possibly cancer. Importantly, these two mechanisms appear to be interacting with each other. However, there is a lack of data on the interplay of macrophage and mesothelium especially in vivo. Since fibrous nanomaterials present potential applications in various fields, it is necessary to develop standard evaluation methods to minimize risks for human health. © 2010 Elsevier Inc.

DOI： 10.1016/j.abb.2010.06.015

Genome-Scale Approaches to Investigate Oxidative DNA Damage 査読有り国際誌

Akatsuka Shinya, Toyokuni Shinya

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 47 巻 ( 2 ) 頁： 91 - 97 2010年9月

Genome-Scale Approaches to Investigate Oxidative DNA Damage 査読有り

Shinya Akatsuka, Shinya Toyokuni

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 47 巻 ( 2 ) 頁： 91 - 97 2010年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

In the trend of biological science after the completion of the human genome project, appreciation of an organism as a system rather than the sum of many molecular functions is necessary. On the investigation of DNA damage and repair, therefore, the orientation toward systematic and comprehensive genome-scale approaches is rapidly growing. The immuno-precipitation-based technique combined with high-density microarrays is one of the promising methods to provide access to such novel research strategies. We propose this sort of research area as oxygenomics.

DOI： 10.3164/jcbn.10-38R

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Genome-scale approaches to investigate oxidative DNA damage

Akatsuka S., Toyokuni S.

Journal of Clinical Biochemistry and Nutrition 47 巻 ( 2 ) 頁： 91 - 97 2010年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Biochemistry and Nutrition

In the trend of biological science after the completion of the human genome project, appreciation of an organism as a system rather than the sum of many molecular functions is necessary. On the investigation of DNA damage and repair, therefore, the orientation toward systematic and comprehensive genome-scale approaches is rapidly growing. The immunoprecipitation-based technique combined with high-density microarrays is one of the promising methods to provide access to such novel research strategies. We propose this sort of research area as oxygenomics.

DOI： 10.3164/jcbn.10-38R

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PubMed

CiNii Research

Suppression of SLC11A2 expression is essential to maintain duodenal integrity during dietary iron overload. 査読有り国際誌 Open Access

Shirase T, Mori K, Okazaki Y, Itoh K, Yamamoto M, Tabuchi M, Kishi F, Jiang L, Akatsuka S, Nakao K, Toyokuni S

The American journal of pathology 177 巻 ( 2 ) 頁： 677 - 85 2010年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Pathology

Iron is essential for the survival of mammals, but iron overload causes fibrosis and carcinogenesis. Reduced iron absorption and regulated release into circulation in duodenal mucosa constitute two major mechanisms of protection against dietary iron overload; however, their relative contribution remains elusive. To study the significance of the former process, we generated SLC11A2 transgenic mice (TGs) under the control of the chicken β-actin promoter. TGs were viable and fertile, and displayed no overt abnormalities up to 20 months. No significant difference in iron concentration was observed in major solid organs between TGs and their wild-type littermates, suggesting that increased number of iron transporters does not lead to increased iron absorption. To test the sensitivity to iron overload, TGs and wild-type mice were fed with an iron-rich diet containing 2% ferric citrate. Iron supplementation caused suppression of endogenous duodenal SLC11A2 expression, down-regulation of duodenal ferroportin, and overexpression of hepatic hepcidin, precluding excessive iron uptake both in the TGs and wild-type mice. However, iron-treated TGs revealed increased mortality, resulting from oxidative mucosal damage leading to hemorrhagic erosion throughout the whole intestinal area. These findings suggest that reduced iron release from duodenal cells into circulation plays a role in mitigating excessive iron uptake from the diet and that finely regulated duodenal absorption is essential to protect intestinal mucosa from iron-induced oxidative damage. Copyright © American Society for Investigative Pathology.

DOI： 10.2353/ajpath.2010.090823

TOWARD A NEW ERA OF THE NAGOYA JOURNAL OF MEDICAL SCIENCE: MESSAGE FROM THE NEW EDITOR-IN-CHIEF 国際誌 Open Access

Toyokuni Shinya

NAGOYA JOURNAL OF MEDICAL SCIENCE 72 巻 ( 3-4 ) 頁： 107 - 109 2010年8月

Toward a new era of the Nagoya journal of medical science: message from the new editor-in-chief. Open Access

Toyokuni S

Nagoya journal of medical science 72 巻 ( 3-4 ) 頁： 107 - 9 2010年8月

Toward a new era of the Nagoya journal of medical science: message from the new editor-in-chief. 査読有り国際誌 Open Access

Toyokuni S.

Nagoya journal of medical science 72 巻 ( 3-4 ) 頁： 107 - 109 2010年8月

Lipid peroxidation generates body odor component trans-2-nonenal covalently bound to protein in vivo. 査読有り国際誌 Open Access

Ishino K, Wakita C, Shibata T, Toyokuni S, Machida S, Matsuda S, Matsuda T, Uchida K

The Journal of biological chemistry 285 巻 ( 20 ) 頁： 15302 - 15313 2010年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

trans-2-Nonenal is an unsaturated aldehyde with an unpleasant greasy and grassy odor endogenously generated during the peroxidation of polyunsaturated fatty acids. 2-Nonenal covalently modified human serum albumin through a reaction in which the aldehyde preferentially reacted with the lysine residues. Modified proteins were immunogenic, and a specific monoclonal antibody (mAb) 27Q4 that cross-reacted with the protein covalently modified with 2-nonenal was raised from mouse. To verify the presence of the protein-bound 2-nonenal in vivo, the mAb 27Q4 against the 2-nonenal-modified keyhole limpet hemocyanin was raised. It was found that a novel 2-nonenal-lysine adduct, cis- and trans-N∈-3-[(hept-1-enyl)-4-hexylpyridinium] lysine (HHP-lysine), constitutes an epitope of the antibody. The immunoreactive materials with mAb 27Q4 were detected in the kidney of rats exposed to ferric nitrilotriacetate, an iron chelate that induces free radical-mediated oxidative tissue damage. Using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry, we also established a highly sensitive method for detection of the cis- and trans-HHP-lysine and confirmed that the 2-nonenallysine adducts were indeed formed during the lipid peroxidation- mediated modification of protein in vitro and in vivo. Furthermore, we examined the involvement of the scavenger receptor lectin-like oxidized low density lipoprotein receptor-1 in the recognition of 2-nonenal-modified proteins and established that the receptor recognized the HHP-lysine adducts as a ligand. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M109.068023

A Novel Method for Efficient Collection of Normal Mesothelial Cells In Vivo 査読有り国際誌

Jiang Li, Yamashita Yoriko, Toyokuni Shinya

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 46 巻 ( 3 ) 頁： 265 - 268 2010年5月

A Novel Method for Efficient Collection of Normal Mesothelial Cells In Vivo 査読有り

Li Jiang, Yoriko Yamashita, Shinya Toyokuni

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 46 巻 ( 3 ) 頁： 265 - 268 2010年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

Asbestos-induced mesothelioma is a challenging social problem in many countries, and oxidative stress via iron is closely associated with its carcinogenesis. Mesothelioma is thought to originate from the mesothelial cells that cover the somatic cavity such as pleural, pericardial and peritoneal cavities. They are single layered and so flat that it is extremely difficult to obtain pure mesothelial cells as control samples from experimental animals. Here we describe a novel method to collect mesothelial cells from animals by the use of simple equipments. Surface of the most organs including lung, spleen and liver are covered with a single layer of mesothelial cells. Scraping the surface of those organs with razor blades after snap-freeze in liquid nitrogen satisfactorily confers almost pure population of mesothelial cells. This simple method would be helpful for obtaining mesothelial control samples from animals to elucidate the molecular mechanisms of a variety of mesothelial pathology.

DOI： 10.3164/jcbn.10-01

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A novel method for efficient collection of normal mesothelial cells in vivo

Jiang L., Yamashita Y., Toyokuni S.

Journal of Clinical Biochemistry and Nutrition 46 巻 ( 3 ) 頁： 265 - 268 2010年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Biochemistry and Nutrition

DOI： 10.3164/jcbn.10-01

Scopus

PubMed

CiNii Research

リンパ腫ゲノムにおけるマイクロサテライト多型不安定性集積の空間統計学解析

鶴山竜昭, リチャード・カシンスキー, 赤塚慎也, 今井裕紀子, 竹内晴哉, 尾関宗孝, 奥野知子, 豊國伸哉, 玉木敬二

日本法医学雑誌 64 巻 ( 1 ) 頁： 54 - 54 2010年5月

n-3 polyunsaturated fatty acids promote apoptosis in oxidatively stressed transgenic mouse models 国際誌

Fan, YY; Toyokuni, S; Callaway, ES; Ran, Q; Lupton, JR; Chapkin, RS

CANCER RESEARCH 70 巻 2010年4月

A Quantitative trait locus responsible for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability

KASZYNSKI Richard H., AKATSUKA Shinya, HIRATSUKA Takuya, JIN Guang, OZEKI Munetaka, OKUNO Tomoko, NAKAMURA Takuro, MANABE Toshiaki, TAKAKUWA Tetsuya, HIAI Hiroshi, TOYOKUNI Shinya, TAMAKI Keiji, TSURUYAMA Tatsuaki

Cancer science 101 巻 ( 3 ) 頁： 800 - 805 2010年3月

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. 査読有り国際誌 Open Access

Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, Takahashi T, Toyokuni S

Laboratory investigation; a journal of technical methods and pathology 90 巻 ( 3 ) 頁： 360 - 73 2010年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Laboratory Investigation

In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by microarray. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2′-deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion. © 2010 USCAP, Inc All rights reserved.

DOI： 10.1038/labinvest.2009.140

A quantitative trait locus responsible for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability. 査読有り国際共著国際誌 Open Access

Kaszynski RH, Akatsuka S, Hiratsuka T, Jin G, Ozeki M, Okuno T, Nakamura T, Manabe T, Takakuwa T, Hiai H, Toyokuni S, Tamaki K, Tsuruyama T

Cancer science 101 巻 ( 3 ) 頁： 800 - 5 2010年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Science

While the molecular mechanisms underlying microsatellite instability (MSI) have been exhaustively investigated, identifying the patterns of MSI distribution within diverse cancer genomes has remained an elusive issue. In the present study, we conducted genome-wide MSI screening in B-cell lymphoblastic lymphomas (B-LBL) which spontaneously develop in the SL/Kh strain of mice. Tumor samples harvested from 16 mice were investigated using a framework map consisting of 150 microsatellite markers spaced at increments of roughly 0.5-3.0 centimorgans, spanning the entirety of mouse chromosomes (mus musculus chromosomes [MMU]) 3-6. MMU3 contains a quantitative trait locus (QTL), Bomb1 (bone marrow pre-B1), known to induce an aberrant expansion of pre-B cells in bone marrow prior to the onset of B-LBL in SL/Kh mice. The remaining chromosomes were selected on the basis of those most closely resembling MMU3 in terms of total estimated length (maximum variance 10 Mb). MSI was confirmed at 2≤ markers in DNA derived from tumor tissues in 15 SL/Kh mice (93.7%), while healthy splenic DNA samples screened in parallel were consistently negative for MSI. The overall MSI incidence was significantly higher on MMU3 compared with MMU4-6 (P = 0.031). Additionally, by applying spatial point pattern analysis combined with a 1-D version of Ripley's K-function, we successfully demonstrated the predilection of MSI-susceptible loci to structure a massive cluster within the Bomb1 locus. Our study is the first to suggest that a QTL concomitantly serves as a hotspot for MSI-susceptible loci and sheds new light on somatic cancer genetics. © 2010 Japanese Cancer Association.

DOI： 10.1111/j.1349-7006.2009.01437.x

前駆B芽球性リンパ腫におけるマイクロサテライト不安定性解析とポイントパターン解析の応用

鶴山竜昭, リチャード・カシンスキー, 赤塚慎也, 中村卓郎, 真鍋敏明, 日合弘, 玉木敬二, 豊國伸哉

日本病理学会会誌 99 巻 ( 1 ) 頁： 217 - 217 2010年3月

平成20年度学術大会科学技術振興研究発表「悪性中皮腫」より : 概要と基礎研究からのアプローチ

大槻剛巳, 中野孝司, 長谷川誠紀, 岡田守人, 辻村亨, 関戸好孝, 豊國伸哉, 西本寛, 福岡和也, 田中文啓

日本職業・災害医学会会誌 = Japanese journal of occupational medicine and traumatology 58 巻 ( 1 ) 頁： 1 - 8 2010年1月

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