Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Possible involvement of iron-induced oxidative insults in neurodegeneration. Reviewed

Asano T, Koike M, Sakata S, Takeda Y, Nakagawa T, Hatano T, Ohshi S, Funayama M, Yoshimi K, Sanuma M, Toyokuni S, Mochizuki H, Uchiyama Y, Hattori N and Iwai K.

Neurosci Lett Vol. 588 page： 29-35 2015

Receptor role of annexin A2 in the mesothelial endocytosis of crocidolite fibers. Reviewed

Yamashita K, Nagai H and Toyokuni S.

Lab Invest Vol. 95 page： 749-764 2015

Minimal inflammogenicity of pristine single-wall carbon nanotubes. Reviewed

Toyokuni S, Jiang L, Kitaura R and Shinohara S.

Nagoya J Med Sci Vol. 77 page： 195-202 2015

Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. Reviewed

Funahashi F, Okazaki Y, Ito D, Asakawa A, Nagai H, Tajima M and Toyokuni S.

J Clin Biochem Nutr 56: 111-117, 2015. Vol. 56 page： 111-117 2015

Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders. Reviewed

Hattori Y, Mukaide T, Jiang L, Kotani T, Tsuda H, Mano Y, Sumigama S, Hirayama T, Nagasawa H, Kikkawa F and Toyokuni S.

J Clin Biochem Nutr 56: 57-63, 2015. Vol. 56 page： 57-63 2015

Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Reviewed

Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M and Takahashi S.

Mod Pathol Vol. 28 page： 111-117 2015

A trial to find appropriate animal models of dichloropropane-induced cholangiocarcinoma based on the hepatic distribution of glutathione S-transferases. Reviewed

Zhang L, Zong C, Ichihara S, Naito H, Toyokuni S, Kumagai S, Ichihara G.

J Occup Health. Vol. 57 ( 6 ) page： 548-554 2015

A trial to find appropriate animal models of dichloropropane-induced cholangiocarcinoma based on the hepatic distribution of glutathione S-transferases International journal

Zhang Lingyi, Zong Cai, Ichihara Sahoko, Naito Hisao, Toyokuni Shinya, Kumagai Shinji, Ichihara Gaku

Journal of Occupational Health Vol. 57 ( 6 ) page： 548 - 554 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Society for Occupational Health

Objectives: It has been reported that 1,2-Dichloropropane (DCP) induced cholangiocarcinoma (CCA) in offset color proof-printing workers. However, exposure to DCP by inhalation or gavage for 2 year did not induce CCA in mice and rats. The present study mapped the hepatic distribution of GST, which is known to activate dihalogenated alkanes, and proliferative and fibrotic changes in bile ducts in various species to find the most appropriate animal model of DCP-induced CCA. Methods: First, 12 each of C57BL/6J mice, Balb/cA mice, F344 rats, Syrian hamsters, and guinea pigs were divided into four equal groups and exposed to DCP at 0, 300, 1,000, or 3,000 ppm 8 hours/day for 7 days. Second, 32 Balb/cA mice and 32 Syrian hamsters were each divided into four equal groups and exposed to DCP at 0, 200, 400, and 800 ppm 6 hours/day for 14 days. After the last exposure, the animals were decapitated, and the livers were dissected out for histopathological evaluation. Immunostaining was conducted to determine the distribution of GSTT1, GSTM1, and GSTPi, as well as the expression of proliferation marker Ki67. Results: GSTT1, GSTM1, and GSTPi were expressed in both hepatocytes and bile duct cells in all control and exposed animals. There was no clear difference in the expression of Ki67 between the exposed groups and the control. No fibrotic changes were observed in any species or strains examined. Conclusions: Expression of GSTT1 or other GST isozymes might not explain the difference in sensitivity of hepatocytes and the bile duct to DCP between humans and rodents.(J Occup Health 2015; 57: 548–554)

DOI： 10.1539/joh.15-0085-oa

Chemical conversion of human fibroblasts into neuronal cells: dawn of future clinical trials. Invited International journal

Toyokuni S

J Clin Biochem Nutr Vol. 56 page： 165 2015

Application of intermittent microwave irradiation to western blot analysis. Reviewed International journal

Liu YT, Toyokuni S

Methods Mol Biol Vol. 1314 page： 185-190 2015

Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury International journal

Y. Hattori, T. Kotani, H. Tsuda, Y. Mano, L. Tu, H. Li, S. Hirako, T. Ushida, K. Imai, T. Nakano, Y. Sato, R. Miki, S. Sumigama, A. Iwase, S. Toyokuni, F. Kikkawa

FREE RADICAL RESEARCH Vol. 49 ( 8 ) page： 1026 - 37 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Maternal inflammation is associated with spontaneous preterm birth and respiratory impairment among premature infants. Recently, molecular hydrogen (H-2) has been reported to have a suppressive effect on oxidative stress and infl ammation. The aim of this study was to evaluate the effects of H-2 on fetal lung injury caused by maternal infl ammation. Cell viability and the production of interleukin-6 (IL-6) and reactive oxygen species (ROS) were examined by treatment with lipopolysaccharide (LPS) contained in ordinal or H-2-rich medium (HM) using a human lung epithelial cell line, A549. Pregnant Sprague Dawley rats were divided into three groups: Control, LPS, and HW + LPS groups. Rats were injected with phosphate-buffered saline (Control) or LPS intraperitoneally (LPS) on gestational day 19 and provided H-2 water (HW) ad libitum for 24 h before LPS injection (HW + LPS). Fetal lung samples were collected on day 20, and the levels of apoptosis, oxidative damage, IL-6, and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry. The number of apoptotic cells, and levels of ROS and IL-6 were significantly increased by LPS treatment, and repressed following cultured with HM in A549 cells. In the rat models, the population positive for cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine, IL-6, and VEGF was significantly increased in the LPS group compared with that observed in the Control group and significantly decreased in the HW + LPS group. In this study, LPS administration induced apoptosis and oxidative damage in fetal lung cells that was ameliorated by maternal H-2 intake. Antenatal H-2 administration may decrease the pulmonary mobility associated with infl ammation in premature infants.

DOI： 10.3109/10715762.2015.1038257

Minimal inflammogenicity of pristine single-wall carbon nanotubes International journal

Toyokuni S., Jiang L., Kitaura R., Shinohara H.

Nagoya Journal of Medical Science Vol. 77 ( 1-2 ) page： 195 - 202 2015

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi-wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 μg/cm2 SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low-risk material with respect to mesothelial carcinogenesis.

Scopus

Application of Intermittent Microwave Irradiation to Western Blot Analysis. International journal

Yu-Ting Liu, Shinya Toyokuni

Methods in molecular biology (Clifton, N.J.) Vol. 1314 page： 185 - 190 2015

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

We established a shortened protocol for Western blot analysis using intermittent microwave irradiation. With this method, the procedure is completed within 1 h after applying the primary antibody, and thus greatly saves time. This procedure appears to be applicable to any antibody based on our experience of several years.

DOI： 10.1007/978-1-4939-2718-0_20

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Receptor role of annexin A2 in the mesothelial endocytosis of crocidolite fibers. Reviewed

Yamashita K, Nagai H, Toyokuni S

Lab Invest Vol. 95 page： 749-764 2015

Hepatic distribution of GST cannot explain the gap between human and rodents for induction of cholangiocarcioma following exposure to dichloropropane

ZHANG Lingyi, ZONG Cai, ICHIHARA Sahoko, NAITO Hisao, TOYOKUNI Shinya, KUMAGAI Shinji, ICHIHARA Gaku

Annual Meeting of the Japanese Society of Toxicology Vol. 42 ( 0 ) page： P - 165 2015

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Toxicology

Purpose: 1,2-Dichloropropane(DCP) is thought to induce cholangiocarcinoma(CCA) among Japanese printing workers in 2013. However no studies have shown DCP-induced CCA in rodents. Five kinds of rodents were exposed to DCP to find an appropriate animal model for DCP-induced CCA. Methods: First, 12 C57BL/6J mice, Balb/cA mice, F344 rats, Syrian Hamsters and Guinea Pigs were divided into 4 groups equally and exposed to DCP at 0, 300, 1000 and 3000 ppm respectively. Then 32 Balb/cA mice and Syrian Hamsters were divvied into 4 groups equally and exposed to DCP at 0, 200, 400 and 800ppm respectively. After the last exposure livers were dissected out for immunohistochemistry with anti- GSTT1, GSTM1, GSTPi antibodies. Result: Either in control or exposed group all of the animals expressed GSTT1 both at liver cells and bile duct cells. Conclusion: GSTT1 expression cannot explain the gap between human and rodents in the case of DCP inducing CCA.

DOI： 10.14869/toxpt.42.1.0_P-165

CiNii Research

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Elucidation of asbestos-induced mesothelial carcinogenesis and risk assessment of nanomaterials

TOYOKUNI Shinya

Annual Meeting of the Japanese Society of Toxicology Vol. 42 ( 0 ) page： S4 - 2 2015

Establishment of murine model for neurotoxicity of 1-bromopropane, an alternative to ozone-depleting solvents

ZONG Cai, GARNER Edwin, HUANG Chin-Yen, ZHANG Lingyi, ZHANG Xiao, SAKURAI Toshihiro, TOYOKUNI Shinya, ICHIHARA Sahoko, ICHIHARA Gaku

Annual Meeting of the Japanese Society of Toxicology Vol. 42 ( 0 ) page： P - 13 2015

鉄過剰症による発がんの分子機構　特集：鉄代謝制御機構と鉄過剰症

豊國伸哉

病理と臨床 Vol. 70 page： 337 - 242 2015

Minimal inflammogenicity of pristine single-wall carbon nanotubes Reviewed International journal

Toyokuni S

Nagoya Journal of Medical Science Vol. 77 ( 1-2 ) page： 195 - 202 2015

Plasma Medical Science for Cancer Therapy: Toward Cancer Therapy Using Nonthermal Atmospheric Pressure Plasma

Hiromasa Tanaka, Masaaki Mizuno, Kenji Ishikawa, Keigo Takeda, Kae Nakamura, Fumi Utsumi, Hiroaki Kajiyama, Hiroyuki Kano, Yasumasa Okazaki, Shinnya Toyokuni, Shoichi Maruyama, Fumitaka Kikkawa, Masaru Hori

IEEE TRANSACTIONS ON PLASMA SCIENCE Vol. 42 ( 12 ) page： 3760 - 3764 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC

We have been developing novel ultrahigh density atmospheric pressure plasma sources and succeeded in the selective killing ovarian cancer cells against normal ones. Furthermore, we have found out the plasma- activated medium (PAM) also killed glioblastoma brain tumor cells selectively against normal ones and the chemical products in the PAM have long lifetime healing effects. To clarify the mechanism, interactions of plasma with the organism and the medium where the organism belongs were investigated on the viewpoint of intracellular molecular mechanism.

DOI： 10.1109/TPS.2014.2353659

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Papers - TOYOKUNI Shinya