Analysis of molecular and cellular targets in neurotoxicity of alternatives to ozone-depleting substances and establishment of biomarkers for the central nervous toxicity

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390160
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Nagoya University
• Principal Investigator: ICHIHARA Gaku Nagoya University, 大学院・医学系研究科, 准教授 (90252238)
• Co-Investigator(Kenkyū-buntansha): ICHIHARA Sahoko 三重大学, 生命科学研究支援センター, 准教授 (20378326)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Teruyuki 東京大学, 大学院・医学系研究科, 准教授 (10246647) ; ITO Hidenori 愛知県コロニー発達障害研究所, 神経制御, 研究員 (40311443) ; TSUKAMURA Hiroko 名古屋大学, 大学院・生命農学研究科, 准教授 (00212051) ; IWAHASHI Hitoshi 産業技術総合研究所, 主任研究員 (60356540) ; OZAKI Noriyuki 名古屋大学, 医学系研究科, 准教授 (40244371) ; SUGIURA Yasuo 名古屋大学, 医学系研究科, 理事 (50093042) ; YAMAMOTO Toshimichi 名古屋大学, 医学系研究科, 准教授 (50260592)
• Project Period (FY): 2007 – 2009
• Keywords: ブロモプロパン / 神経毒性 / バイオマーカー

Research Abstract

The present study revealed that the cerebrum and hippocampus are the most susceptible brain regions to 1-bromopropane exposure, regarding suppression of gene expression of neurotransmitter receptors. Experiments using three inbred mice and Nrf2-null mice showed that CYPIIE1 and glutathione pathway contribute to the susceptibility and oxidative stress is involved in the toxicity of 1-bromopropane. Moreover, study on protein adducts revealed that cysteine in the protein is one of the molecular targets of 1-bromopropane.

Research Products

• [Journal Article] Increased susceptibility of Nrf2 null mice to 1-bromopropane-induced hepatotoxicity (2010)
  • Author(s): Liu F, Ichihara S, Valentine WM, Itoh K, Yamamoto M, Mohideen SS, Kitoh J, Ichihara G
  • Journal Title: Toxicological Sciences (in press)
  • Peer Reviewed
• [Journal Article] Comparative study on susceptibility to 1-bromopropane in three mice strains (2009)
  • Author(s): Liu F, Ichihara S, Mohideen SS, Sai U, Kitoh J, Ichihara G.
  • Journal Title: Toxicological Sciences 112 Pages: 100-10
  • Peer Reviewed
• [Journal Article] Changes in neurotransmitter receptor expression levels in rat brain after 4-week exposure to 1-bromopropane (2009)
  • Author(s): Mohideen SS, Ichihara S, Banu S, Liu F, Kitoh J, Ichihara G
  • Journal Title: Neurotoxicology 30 Pages: 1078-83
  • Peer Reviewed
• [Journal Article] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor (2009)
  • Author(s): Ichihara S, Yamada Y, Gonzalez FJ, Nakajima T, Murohara T, Ichihara G
  • Journal Title: Biochem Biophys Res Commun 381 Pages: 44-49
  • Peer Reviewed
• [Journal Article] Melatonin pretreatment attenuates 2-bromopropane-induced testicular toxicity in rats (2009)
  • Author(s): Huang F, Ning H, Xin QQ, Huang Y, Wang H, Zhang ZH, Xu DX, Ichihara G, Ye DQ
  • Journal Title: Biochem Biophys Res Commun 256 Pages: 75-82
  • Peer Reviewed
• [Journal Article] Nanoparticles:-one word: a multiplicity of different hazards (2009)
  • Author(s): Donaldson K, Oberdorster G, Ichihara G, Maynard A, Stone V, Borm P, Aitken R
  • Journal Title: Biochem Biophys Res Commun 3 Pages: 263-264
  • Peer Reviewed
• [Journal Article] 有機溶剤中毒と尿検査 (2009)
  • Author(s): 市原学
  • Journal Title: 総合臨床 58 Pages: 1269-1271
• [Journal Article] Carbon Nanotubes in historical and future perspective: summary of an extended session at Carbon 2008 in Nagano (JP) (2008)
  • Author(s): Endo M, Tsuruoka S, Ichihara G
  • Journal Title: Part Fibre Toxicol 5 Pages: 21
  • Peer Reviewed
• [Journal Article] In vitro cytotoxicity and oxidative damage effects of multi-wall carbon nanotube on RAW246. 7 macrophages (2008)
  • Author(s): Liu Y, Song W, Li W, Ichihara G
  • Journal Title: Wei Sheng Yan Jiu 37(in Chinese) Pages: 281-4
  • Peer Reviewed
• [Journal Article] Induction of mesothelioma in p53+/-mouse by intraperitoneal application of multi-wall carbon nanotube (2008)
  • Author(s): Ichihara G, Castranova V, Tanioka A, Miyazawa K. Re
  • Journal Title: J Toxicol Sci 33 Pages: 381-2
  • Peer Reviewed
• [Journal Article] Methylation of dimethyltin in mice and rats (2008)
  • Author(s): Furuhashi K, Ogawa M, Suzuki Y, Endo Y, Kim Y, Ichihara G
  • Journal Title: Chemical Research in Toxicology 21 Pages: 467-71
  • Peer Reviewed
• [Journal Article] Molecular mechanism of trichloroethylene-induced hepatoxicity mediated by CYP2E1 (2008)
  • Author(s): Ramdhan DH, Kamijima M, Yamda N, Ito Y, Yanagiba Y, Nakamura D, Okamura A, Ichihara G, Aoyama T, Gonzalez FJ, Nakajima T
  • Journal Title: Toxicol Appli Pharmacol 231 Pages: 300-7
  • Peer Reviewed
• [Journal Article] Chemopreventive Effect of Selenium-Enriched Japanese Radish Sprout against Breast Cancer Induced by 12-Dimethylbenz[a]anthracene in Rats (2007)
  • Author(s): Yamanoshita O, Ichihara S, Hama H, Ichihara G, Chiba M, Kamijima M, Takeda I, Nakajima T
  • Journal Title: Tohoku J Exp Med 212 Pages: 191-8
  • Peer Reviewed
• [Journal Article] Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway (2007)
  • Author(s): Ito Y, Yamanoshita O, Asaeda N, Tagawa Y, Lee C, Aoyama T, Ichihara G, Furuhashi K, Kamijima M, Gonzalez FJ, Nakajima T
  • Journal Title: J Occup Health 49 Pages: 172-82
  • Peer Reviewed
• [Journal Article] A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis (2007)
  • Author(s): Ichihara S, Yamada Y, Ichihara G, Nakajima T, Kondo T, Gonzalez FJ, Murohara T
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 1297-1304
  • Peer Reviewed
• [Journal Article] Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity (2007)
  • Author(s): Ichihara S, Yamada Y, Kawai Y, Osawa T, Furuhashi K, Duan Z, Ichihara G
  • Journal Title: Biochem Biophys Res Commun 359 Pages: 27-33
  • Peer Reviewed
• [Journal Article] Differential cardiovascular effects of endotoxin derived from Escherichia coli or Pseudomonas aeruginosa (2007)
  • Author(s): Matsushita A, Iwase M, Kato Y, Ichihara S, Ichihara G, Kimata H, Hayashi K, Hashimoto K, Yokoi T, Noda A, Koike Y, Yokota M, Nagata K
  • Journal Title: Exp Anim 56 Pages: 339-48
  • Peer Reviewed
• [Journal Article] Globin S-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure (2007)
  • Author(s): Valentine H, Amarnath K, Amarnath V, Li W, Ding X, Valentine WM, Ichihara G
  • Journal Title: Toxicological Sciences 98 Pages: 427-35
  • Peer Reviewed
• [Journal Article] Reversibility of the adverse effects of 1-bromopropane exposure in rats (2007)
  • Author(s): Banu S, Ichihara S, Huang F, Ito H, Inaguma Y, Furuhashi K, Fukunaga Y, Wang Q, Kitoh J, Ando H, Kikkawa F, Ichihara G
  • Journal Title: Toxicological Sciences 100 Pages: 504-12
  • Peer Reviewed
• [Presentation] Nrf2 null mice are more susceptible to 1-bromopropane-induced hepatotoxicity (2010)
  • Author(s): Fang Liu, Sahoko Ichihara, William M. Valentine, Ken Itoh, Masayuki Yamamoto, Sahabudeen Sheik Mohideen, Junzoh Kitoh, Gaku Ichihara
  • Organizer: The 49th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Salt lake city, USA
  • Year and Date: 20100307-20100311
• [Presentation] N-acetyl-L-cysteine prevents the toxic effects of hyperphosphatemia and hypozincemia on the testicular function in WKY, but not in SHR/NDmcr-cp, a model of metabolic syndrome (2010)
  • Author(s): Yuka Suzuki, Sahoko Ichihara, Ai Kato, Takanori Yamaguchi, Yoshiji Yamada, Gaku Ichihara
  • Organizer: The 49th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Salt lake city, USA
  • Year and Date: 20100307-20100311
• [Presentation] Dose-dependent neurological and hematological effects of 1-bromopropane exposure on workers (2009)
  • Author(s): Ichihara G., Li W, Shibata E, Zhou Z, Ichihara S, Wang Q, Li J, Ding X, Takeuchi Y
  • Organizer: The 29th International Congress on Occupational Health
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 20090322-20090327
• [Presentation] Occupational Health Survey on workers handling titanium dioxide (2009)
  • Author(s): Ichihara S, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Wang Q, Cui U, Hata N, Ichihara G
  • Organizer: The 29th International Congress on Occupational Health
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 20090322-20090327
• [Presentation] Exposure assessment and health examination of workers handling titanium dioxide (2009)
  • Author(s): Ichihara G, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Sai U, Hata N, Wang Q, Ichihara S
  • Organizer: The 48th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Baltimore, USA
  • Year and Date: 20090315-20090319
• [Presentation] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on aryl hydrocarbon receptor (2009)
  • Author(s): Ichihara S, Yamada Y, Ichihara G, Nakajima T, Gonzalez E. J, Murohara T
  • Organizer: The 48th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Baltimore, USA
  • Year and Date: 20090315-20090319
• [Presentation] Exposure assessment and evaluation of health status in workers handling titanium dioxide (2009)
  • Author(s): Gaku Ichihara, Weihua Li, Yuji Fujitani, Sahoko Ichihara, Xuncheng Ding, Ying Liu, Qiangyi Wang, Uka Sai, Natsumi Hata, Takahiro Kobayashi
  • Organizer: The 4th International Conference on Nanotechnology
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2009-08-29
• [Presentation] Epidemiological Study on workers handling titanium dioxide (2009)
  • Author(s): Ichihara G
  • Organizer: Symposium on the social acceptance of nanomaterials
  • Place of Presentation: National Institute for Materials Science, Tsukuba, Japan
  • Year and Date: 2009-07-24
• [Presentation] Assessment of exposure and health status in workers handling titanium dioxide (2008)
  • Author(s): Ichihara G, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Wang Q, Cui U, Hata N, Ichihara S
  • Organizer: Internatoinal Conference on safe production and use of nanomaterials
  • Place of Presentation: Minatec, Grenoble, France
  • Year and Date: 20081103-20081107
• [Presentation] Occupational Health Survey on workers handling titanium dioxide (2008)
  • Author(s): Ichihara G, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Wang Q, Cui U, Hata N, Ichihara S
  • Organizer: The 45th Congress of the European Societies of Toxicology
  • Place of Presentation: Rhodes, Greece
  • Year and Date: 20081005-20081008
• [Presentation] Recent studies of bromopropane toxicity-animal studies and newly found human cases in United States (2008)
  • Author(s): Ichihara G
  • Organizer: China-Japan Collaboration Workshop "Environmental Health and Safety Research on new manufactured materials"
  • Place of Presentation: Shanghai, China
  • Year and Date: 20080730-20080731
• [Presentation] Microarray study on bromopropane toxicity (2008)
  • Author(s): Ichihara G
  • Organizer: China-Japan Collaboration Workshop "Environmental Health and Safety Research on new manufactured materials"
  • Place of Presentation: Shanghai, China
  • Year and Date: 20080730-20080731
• [Presentation] International collaboration and coordination of nanotoxicology research (2008)
  • Author(s): Ichihara G
  • Organizer: China-Japan Collaboration Workshop "Environmental Health and Safety Research on new manufactured materials"
  • Place of Presentation: Shanghai, China
  • Year and Date: 20080730-20080731
• [Presentation] Methylation of dimethyltin in mice and rats (2008)
  • Author(s): Furuhashi K, Ogawa M, Suzuki Y, Endo Y, Ichihara G
  • Organizer: The 47th Annual Meeting of Society of Toxicology
  • Place of Presentation: Seattle, Washington, USA
  • Year and Date: 20080316-20080320
• [Presentation] Effect of 1-bromopropane exposure on gene expression of neurotransmitter receptors in rat (2008)
  • Author(s): Sheik Mohideen S, Ichihara S, Liu F, Furuhashi K, Li W, Ichihara G
  • Organizer: The 47th Annual Meeting of Society of Toxicology
  • Place of Presentation: Seattle, Washington, USA
  • Year and Date: 20080316-20080320
• [Presentation] Neurotoxicity and reproductive toxicity of 1-bromopropapane, an alternative to ozone-depleting solvents (2008)
  • Author(s): Ichihara G
  • Organizer: International Conference on "Toxic Exposure Related Biomarker : Genomes and Health Effects"
  • Place of Presentation: National Environmental Engineering Research Institute, Nagpur, India
  • Year and Date: 20080110-20080111
• [Presentation] Animal experiments and human studies in risk assessment of manufactured nanomaterials (2008)
  • Author(s): Ichihara G
  • Organizer: International Workshop at Nagoya University "Recent Progress in EHS Research on Manufactured Nanomaterials. "
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2008-12-12
• [Presentation] Environment, Health and Safety Research on Manufactured Nanomaterials (2007)
  • Author(s): Ichihara G
  • Organizer: The 13th International Symposium on Toxicity Assessment
  • Place of Presentation: Toyama, Japan
  • Year and Date: 20070819-20070824
• [Presentation] DNA microarray study with two dimensional analysis on susceptibility to 1-bromopropane exposure (2007)
  • Author(s): Huang F, Ichihara S, Kitagawa E, Mizugami S, Iwahashi H, Kito J, Furuhashi K, Banu S, Iida M, Ichihara G
  • Organizer: The 11th International Congress of Toxicology
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20070715-20070719
• [Presentation] Dose-dependent effects of 1-bromopropane exposure on workers (2007)
  • Author(s): Li W, Wang Q, Ding X, Shibata E, Takeuchi Y, Valentine W, Ichihara G
  • Organizer: The 18th Korea Japan China Joint Conference on Occupational Health
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 20070520-20070522
• [Presentation] Effect of 1-bromopropane exposure on gene expression of neurotransmitter receptors and exploration of biomarkers for the central nervous system toxicity (2007)
  • Author(s): Sahabudeen S, Ichihara G
  • Organizer: The 24th International Neurotoxicology Conference
  • Place of Presentation: San Antonio, TX, US
  • Year and Date: 20070011-20070014
• [Presentation] Occupational Health Survey on workers handling nano-titanium dioxide (2007)
  • Author(s): Ichihara G
  • Organizer: Roundtable on Nanotechnology and engineered nanoparticles: Research perspectives in Occupational Health and Safety
  • Place of Presentation: Canadian Embassy, Tokyo, Japan
  • Year and Date: 2007-02-12
• [Book] 工業業ナノ素材の環境、健康、安全性研究戦略と労働現場におけるナノ粒子測定、ナノ材料のリスク評価と安全性対策 (2010)
  • Author(s): 市原学
  • Publisher: フロンティア出版