Analysis of arsenic-mediated carcinogenesis and development of a preventive therapy targeting modulation for three-dimensional structure of oncogene products.

2011 Fiscal Year Final Research Report

• Project/Area Number: 20406003
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Nagoya University (2011); Chubu University (2008-2010)
• Principal Investigator: KATO Masashi 名古屋大学, 医学系研究科, 教授 (10281073)
• Co-Investigator(Kenkyū-buntansha): OHGAMI Nobutaka 中部大学, 生命健康科学部, 講師 (80424919) ; KAWAMOTO Yoshiyuki 中部大学, 生命健康科学部, 准教授 (10410664) ; YAMANOSHITA Osamu 中部大学, 生命健康科学部, 講師 (50424924) ; 後藤 友二 中部大学, 生命健康科学部, 助手 (70362522) ; 伊田 みちる 中部大学, 生命健康科学研究所, 助教 (80393148)
• Project Period (FY): 2008 – 2011
• Keywords: ヒ素 / 発癌 / 癌遺伝子産物 / システイン

Research Abstract

It has been reported that arsenic in well drinking water causes various cancers in patients with arsenicosis. Therefore, identification of arsenic-polluted well water is important. Moreover, clarification of mechanisms for arsenic-mediated cancer is also important to develop novel preventive therapies for arsenic-mediated cancers. In this study, we performed international collaboration with several universities in Asian countries and investigated levels of various elements including arsenic. We further showed that arsenic might promote carcinogenesis through cysteine-mediated modulation for three-dimensional structure of oncogene products. Based on the results, we proposed a cysteine-targeted preventive therapy for arsenic-mediated cancer.

Research Products

• [Journal Article] Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water. (2013)
  • Author(s): Kumasaka YM, Yamanoshita O, Shimizu S, Ohnuma S, Furuta A, Yajima I, Nizam S, Khalequzzaman M, Shekhar UH, Nakajima T, Kato M
  • Journal Title: Arch Toxicol Volume: 87 Pages: 439-447
  • Peer Reviewed
• [Journal Article] Exposure to low-dose barium by drinking water causes hearing loss in mice. (2012)
  • Author(s): Ohgami N, Hori S, Ohgami K, Tamura H, Tsuzuki T, Ohnuma S, Kato M.
  • Journal Title: Neurotoxicol Volume: 33(5) Pages: 1276-83
  • Peer Reviewed
• [Journal Article] Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells (2012)
  • Author(s): Yajima I, Uemura N, Nizam S, Khalequzzaman M, Thnag ND, Kumasaka YM, Akhand AA, Shekhar HU, Nakajima T, Kato M.
  • Journal Title: Arch Toxicol Volume: 86(6) Pages: 961-73
  • Peer Reviewed
• [Journal Article] Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase (2011)
  • Author(s): Thang ND, YajimaI, KumasakaMY, Ohnuma S, YanagishitaT, HayashiR, ShekharHU, WatanabeD, KatoM.
  • Journal Title: PLoS ONE Volume: 6(10) Pages: e25636
  • Peer Reviewed
• [Journal Article] Antioxidative effects of cherry leaves extract on tert-butyl hydroperoxide-mediated cytotoxicity through regulation of thioredoxin-2 protein expression level. (2011)
  • Author(s): TaguchiN, UemuraN, GotoY, SakuraM, HaraK, NiwaM, IidaM, YanagishitaT, WatanabeD, KatoM.
  • Journal Title: J Toxicol Environ Health A Volume: 74(18) Pages: 1240-7
  • Peer Reviewed
• [Journal Article] L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects. (2011)
  • Author(s): Kato M, Kumasaka MY, Takeda K, Hossain K, Iida M, Yajima I, Goto Y, Ohgami N.
  • Journal Title: Toxcol In Vitro Volume: 25 Pages: 623-629
  • Peer Reviewed
• [Journal Article] Toxic Elements in Well Water from Malaysia. (2010)
  • Author(s): Kato M, Ohnuma S, Kato Y, Thang D. Nguyen, Yajima I, Hoque Z. Mohammad, Shekhar U. Hossain.
  • Journal Title: Toxicol Environ Chem Volume: 92(9) Pages: 1609-12
  • Peer Reviewed
• [Journal Article] A redox-linked novel pathway for arsenic-mediated RET tyrosine kinase activation. (2010)
  • Author(s): Kato M, Takeda K, Hossain K, Thang D. Nguyen, Kaneko Y, Kumasaka M, Yamanoshita O, Uemura N, Takahashi M, Ohgami N, Kawamoto Y.
  • Journal Title: J Cell Biochem Volume: 110 Pages: 399-407
  • Peer Reviewed
• [Journal Article] 1,4-butanediyl- bismethanethiosulfonate (BMTS) induces reactive oxygen species-mediated apoptotic signals independent of stress-activated MAPK cascade in Jurkat cells. (2009)
  • Author(s): Hossain K, Kawamoto Y, Hamada M, Akhand A, Yanagishita T, Hoque Md. A, Tsuboi H, Kato M, Nakashima I
  • Journal Title: J Cell Biochem Volume: 108(5) Pages: 1059-65
  • Peer Reviewed
• [Journal Article] Arsenic enhances matrix metalloproteinase-14 expression in fibroblasts. (2008)
  • Author(s): Kato M, Hossain K, Iida M, Sato H, Uemura N, Goto Y
  • Journal Title: J Toxicol Environ Healt A Volume: 71(16) Pages: 1053-5
  • Peer Reviewed
• [Presentation] 飲用井戸水の重金属複合汚染による発癌リスクに関する解析 (2013)
  • Author(s): 矢嶋伊知朗、熊坂真由子、Saika Nizam、Md. Khalequzzaman、Hossain U. Shekhar、大沼章子、古田昭男、那須民江、加藤昌志
  • Organizer: 第12回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンスインフォメーションセンター、筑波
  • Year and Date: 20130201-02
• [Presentation] 愛知県とバングラデシュ・ジェソール地区住民の尿中ヒ素化学形態に関する比較研究 (2012)
  • Author(s): 小島美千代・椛島由佳・青山富彦・林留美子・皆川洋子・大沼章子・加藤昌志
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都府(京都大学吉田キャンパス)
  • Year and Date: 20120324-26
• [Presentation] 重金属吸着剤におけるヒ素除去能力の検討 (2010)
  • Author(s): 山ノ下理・大神信孝・大沼章子・林留美子・加藤昌志
  • Organizer: 第80回日本衛生学会学術総会
  • Place of Presentation: 宮城県(仙台国際センター)
  • Year and Date: 20100509-11
• [Presentation] 飲水投与した塩化バリウムが生体内の必須元素レベルに与える影響 (2010)
  • Author(s): 堀創二朗・大神信孝・大沼章子・加藤昌志
  • Organizer: 第80回日本衛生学会学術総会
  • Place of Presentation: 宮城県(仙台国際センター)
  • Year and Date: 20100509-11
• [Presentation] ヒ素によるガン化とその除去に関する解析 (2009)
  • Author(s): 山ノ下理・上村規行・加藤昌志
  • Place of Presentation: 東京都(北里大学)
  • Year and Date: 20090329-0401
• [Book] モデル動物利用マニュアルシリーズ 疾患モデルの作製と利用(分担執筆:第I 部疾患モデルの作成と利用、第2 章多臓器発がんモデル、第7 節 Ret) (2012)
  • Author(s): 加藤昌志・高橋雅英
  • Publisher: 株式会社 エル・アイ・シー
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/medical/1814/1815/kankyouroudoueiseigaku.html
• [Patent(Industrial Property Rights)] 白髪発症モデル動物、白髪発症モデル動物の樹立方法、白髪発症モデル動物の継代方法、白髪発症の研究方法、白髪発症制御手段のスクリーニング方法、白髪発症制御用組成物 (2011)
  • Inventor(s): 加藤昌志
  • Industrial Property Rights Holder: 中部大学
  • Industrial Property Number: 11/988,203
  • Acquisition Date: 2011-09-01
  • Overseas
• [Patent(Industrial Property Rights)] 発癌毒性の評価方法及び発癌予防・治療剤 (2009)
  • Inventor(s): 加藤昌志
  • Industrial Property Rights Holder: 中部大学
  • Industrial Property Number: 特願 2009-241197
  • Filing Date: 2009-10-20