Carcinogenic risk assessment of nano-sized particles

• Project/Area Number: 19590393
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kagawa University
• Principal Investigator: IMAIDA Katsumi Kagawa University, 医学部, 教授 (90160043)
• Co-Investigator(Kenkyū-buntansha): KUNO Toshiya 岐阜大学, 大学院・医学系研究科, 腫瘍病理 (00345779) ; YOKOHIRA Masanao 香川大学, 医学部, 助教 (70403780) ; HASHIMOTO Nozomi 香川大学, 医学部, 助教 (60448371) ; INOUE Tatsushi 香川大学, 医学部, 助教 (80384593)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ナノサイズ粒子 / ラット肝中期発癌試験 / 気管内投与 / 強制胃内投与 / 経静脈投与 / GST-P positive foci / 酸化銅 / 二酸化チタン / ナノサイズ微粒子 / 発がんリスク / 腫瘍 / 肝発がん / 中期発がん性試験法 / ラット / 経気管内投与

Research Abstract

Carcinogenesis of nanoparticles remains uncertain despite nano-sized materials are widely used. In this study, liver carcinogenesis of nano- and micro-sized particles (Copper oxide;CuO, Titanium dioxide ; TiO_2) was examined after exposure of three different routes. Consequently, these results indicate that nanoparticles have promoting potential on the liver carcinogenesis.

Research Products

• [Journal Article] Lack of promoting effects from physical pulmonary collapse in a female A/J mouse lung tumor initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) with remarkable mesothelial cell reactions in the thoracic cavity by the polymer. (2011)
  • Author(s): Yokohira M, Hashimoto N, Yamakawa K, Saoo K, Kuno T, Imaida K.
  • Journal Title: Exp.Toxicol.Pathol. 63 Pages: 181-185
  • Peer Reviewed
• [Journal Article] Risk analysis of environmental chemicals on lung carcinogenesis. (2010)
  • Author(s): Imaida K, Yokohira M, Hashimoto N, Kuno T.
  • Journal Title: Asian Pacific J Cancer Prev 11 Pages: 9-12
  • Peer Reviewed
• [Journal Article] Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions with iron accumulation in female A/J mice. (2010)
  • Author(s): Yokohira M, Hashimoto N, Yamakawa K, Suzuki S, Saoo K, Kuno T, Imaida K.
  • Journal Title: Oncol.Lett. 1 Pages: 273-278
  • Peer Reviewed
• [Journal Article] Molecular analysis of carcinogen induced rodent lung tumors-Invovement of microRNA expression and Kras or EGFR mutation. (2010)
  • Author(s): Yamakawa K, Kuno T, Hashimoto N, Yokohira M, Suzuki S, Nakano Y, Saoo K, Imaida, K.
  • Journal Title: Molecular Medicine Reports 3 Pages: 141-147
  • Peer Reviewed
• [Journal Article] Tumorigenesis of 2-Amino-3,8-dimethylimidazo[4,5-f]qu inoxaline (MeIQx), but not enhancing effects of concomitant high fat diet, on lung carcinogenesis in female A/J mice. (2010)
  • Author(s): Takeuchi H, Saoo K, Yamakawa K, Matsuda Y, Yokohira M, Zeng Y, Kuno T, Totsuka Y, Takahashi M, Wakabayashi K, Imaida K.
  • Journal Title: Oncol.Lett. 1 Pages: 137-142
  • Peer Reviewed
• [Journal Article] Different threshold levels for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) initiation of lung and colon carcinogenesis and the effects of an additional initiation by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice. (2010)
  • Author(s): Suzuki S, Yokohira M, Hashimoto N, Saoo K, Matsuda Y, Yamakawa K, Nakano Y, Kuno T, Imaida K.
  • Journal Title: Molecular Medicine Reports 3 Pages: 301-307
  • Peer Reviewed
• [Journal Article] Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions with iron accumulation in female A/J mice. (2010)
  • Author(s): Yokohira M
  • Journal Title: Oncol.Lett. Volume: 1巻 Pages: 589-594
  • Peer Reviewed
• [Journal Article] A medium-term, rapid rat bioassay model for the detection of carcinogenic potential of chemicals. (2010)
  • Author(s): Tsuda H
  • Journal Title: Toxicol.Pathol. Volume: 38巻 Pages: 182-187
  • Peer Reviewed
• [Journal Article] Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions with iron accumulation in female A/J mice (2010)
  • Author(s): Yokohira M, Hashimoto N, Imaida K, et al.
  • Journal Title: Oncol.Lett. (in press)
• [Journal Article] Lack of promoting effects from physical pulmonary collapse in a female A/J mouse lung tumor initiated with 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) with remarkable mesothelial cell reactions in the thoracic cavity by the polymer (2010)
  • Author(s): Yokohira M, Hashimoto N, Imaida K, et al.
  • Journal Title: Exp.Toxicol.Pathol. (in press)
• [Journal Article] A medium-term, rapid rat bioassay model for the detection of carcinogenic potential of chemicals (2010)
  • Author(s): Tsuda H.
  • Journal Title: Toxicol Pathol. 38 Pages: 182-187
  • Peer Reviewed
• [Journal Article] Lack of modifying effects of intratracheal instillation of quartz or dextran sulfate sodium (DSS) in drinking water on lung tumor development initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice. (2009)
  • Author(s): Yokohira M, Hashimoto N, Yamakawa K, Suzuki S, Saoo K, Kuno T, Imaida K.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 179-185
  • NAID: 10030978156
  • Peer Reviewed
• [Journal Article] Immunohistochemically detected expression of p27kip1 and skp2 predicts survival in patients with intrahepatic cholangiocarcinomas. (2009)
  • Author(s): Hashimoto N, Yachida S, Okano K, Wakabayashi H, Imaida K, Kurokohchi K, Masaki T, Kinoshita H, Tominaga M, Ajiki T, Ku Y, Okabayashi T, Hanazaki K, Hiroi M, Izumi S, Mano S, Okada S, Karasawa V, Maeba V, Suzuki Y.
  • Journal Title: Ann.Surg.Oncol. 16 Pages: 395-403
  • Peer Reviewed
• [Journal Article] Enhancing effects of a high fat diet on 2-amino-3,8-dimethylimidazo[4,5-f]qui noxaline (MeIQx) induced lung tumorigenesis in female A/J mice. (2009)
  • Author(s): Matsuda Y, Takeuchi H, Yokohira M, Saoo K, Hosokawa K, Yamakawa K, Zeng Y, Totsuka Y, Wakabayashi K, Imaida K.
  • Journal Title: Molecular Medicine Reports 2 Pages: 701-706
  • Peer Reviewed
• [Journal Article] carcinogenic bioassay of CuO and TiO2 nanoparticles with intratracheal instillation using F344 male rats. (2009)
  • Author(s): Yokohira M, Hashimoto N, Yamakawa K, Suzuki S, Saoo K, Kuno T, Imaida K. A lung
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 71-78
  • Peer Reviewed
• [Journal Article] An intratracheal instillation bioassay system for detection of lung toxicity due to fine particles in F344 rats. (2009)
  • Author(s): Yokohira M, Kuno T, Yamakawa K, Hashimoto N, Ninomiya F, Suzuki S, Saoo K, Imaida K.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 1-10
  • NAID: 10030977104
  • Peer Reviewed
• [Journal Article] Lack of modifying effects of intra-tracheal instillation of quartz or dextran sulfate sodium (DSS) in drinking water on lung tumor development initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-buta none (NNK) in female A/J mice (2009)
  • Author(s): Yokohira M, Hashimoto N, Imaida K, et al.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 179-185
• [Journal Article] A lung carcinogenic bioassay of CuO and TiO2 nanoparticles with intratracheal instillation using F344 male rats (2009)
  • Author(s): Yokohira M, Hashimoto N, Imaida K, et al.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 71-78
  • NAID: 130000101848
• [Journal Article] An intratracheal instillation bioassay system for detection of lung toxicity due to fine particles in F344 rats (2009)
  • Author(s): Yokohira M, Kuno T, Imaida K, et al.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 1-10
  • NAID: 10030977104
• [Journal Article] Lack of modifying effects of intratracheal instillation of quartz or dextran sulfate sodium (DSS) in drinking water on lung tumor development initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice (2009)
  • Author(s): Yokohira M.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 179-185
  • NAID: 10030978156
  • Peer Reviewed
• [Journal Article] A lung carcinogenic bioassay of CuO and TiO2 nanoparticles with intratracheal instillation using F344 male rats (2009)
  • Author(s): Yokohira M.
  • Journal Title: J.Toxicol.Pathol. 22 Pages: 71-78
  • NAID: 130000101848
  • Peer Reviewed
• [Journal Article] Lack of modifying potential of 8-methoxypsoralen in the promotion or progression stages of lung carcinogenesis in A/J emale ice. (2008)
  • Author(s): Kuno T, Yokohira M, Matsuda Y, Suzuki S, Hashimoto N, Yamakawa K, Saoo K, Imaida K.
  • Journal Title: Oncol.Rep. 20(4) Pages: 767-772
  • Peer Reviewed
• [Journal Article] Establishment of a bioassay model for lung cancer chemoprevention initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice. (2008)
  • Author(s): Yokohira M, Takeuchi H, Saoo K, Matsuda Y, Yamakawa K, Hosokawa K, Kuno T, Imaida K.
  • Journal Title: Exp.Toxicol.Pathol. 60 Pages: 469-473
  • Peer Reviewed
• [Journal Article] Lung toxicity of 16 fine particles on intratracheal instillation in a bioassay model using F344 male rats. (2008)
  • Author(s): Yokohira M, Kuno T, Yamakawa K, Hosokawa K, Matsuda Y, Hashimoto N, Suzuki S, Saoo K, Imaida K.
  • Journal Title: Toxicol.Pathol. 36 Pages: 620-631
  • Peer Reviewed
• [Journal Article] Detection of carcinogenic and modifying potentials by test compounds using amouse lung carcinogenesis bioassay. (2007)
  • Author(s): Imaida K, Yokohira Y, Kuno T.
  • Journal Title: J.Toxicol.Pathol. 20 Pages: 117-123
  • Peer Reviewed
• [Journal Article] Bioassay by intratracheal instillation for detection of lung toxicity due to fine particles in F344 male rats. (2007)
  • Author(s): Yokohira M, Takeuchi H, Yamakawa K, Saoo K, Matsuda Y, Zeng Y, Hosokawa K, Imaida K.
  • Journal Title: Exp.Toxicol.Pathol. 58 Pages: 211-221
  • Peer Reviewed
• [Journal Article] Post-initiation chemopreventive effects of dietary bovine lactoferrin on4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesisin female A/J mice (2007)
  • Author(s): Matsuda Y, Saoo K, Hosokawa K, Yamakawa K, Yokohira M, Zeng Y, Takeuchi H, Imaida, K
  • Journal Title: Cancer Letters 246 Pages: 41-46
  • Peer Reviewed
• [Journal Article] Bioassay by intratracheal instillation for detection of lupg toxicity due to fine particles in F344 male rats (2007)
  • Author(s): Yokohira M, Takeuchi H, Yamakawa K, Saoo K, Matsuda Y, Zeng Y, Hosokawa K, Imaida K
  • Journal Title: Exp Toxicol Pathol. 58 Pages: 211-221
  • Peer Reviewed
• [Journal Article] Overexpression of CYP2A6 in Human Colorectal Tumors (2007)
  • Author(s): Matsuda Y, Saoo K, Yamakawa K, Yokohira M, Suzuki S, Kuno T, Kamataki T, Imaida K.
  • Journal Title: Cancer Sci. 98 Pages: 1582-1585
  • NAID: 10019997476
  • Peer Reviewed
• [Journal Article] Detection of Carcinogenic and Modifying Potentials by Test Compounds Using a Mouse Lung Carcinogenesis Bioassay (2007)
  • Author(s): Imaida K, Yokohira Y, Kuno T
  • Journal Title: J.Toxicol.Pathol. 20 Pages: 117-123
  • NAID: 10025854280
  • Peer Reviewed
• [Journal Article] CYP2A6 overexpression in human lung cancers corelates with a high malignant status (2007)
  • Author(s): Matsuda Y, Yamakawa K, Saoo K, Hosokawa K, Yokohira M, Kuno T, Iwai J, Shirai T, Obika K, Kamataki T, Imaida K
  • Journal Title: Oncol Rep. 18 Pages: 53-57
  • Peer Reviewed
• [Journal Article] 毒性病理学の最近の話題:経気道曝露による肺毒性-喫煙と大気汚染- (2007)
  • Author(s): 今井田 克己、横平 政直
  • Journal Title: 病理と臨床 25 Pages: 769-775
  • Peer Reviewed
• [Presentation] ラット気管内投与によるnicotineの毒性作用 (2011)
  • Author(s): 今井田克己
  • Organizer: 日本毒性病理学会
  • Place of Presentation: 大阪国際交流センター(大阪)(招待講演)
  • Year and Date: 2011-01-27
• [Presentation] Comparison of nano- and micro-sized particles by three different route administrations using a medium-term liver carcinogenesis bioassay in F344 rats. (2009)
  • Author(s): 橋本希, 横平正直, 今井田克己, et al.
  • Organizer: American Association for Cancer Resaech 100^<th> Annual Meeting 2009.
  • Place of Presentation: Colorado Convention Center,(米国)
  • Year and Date: 2009-04-19
• [Presentation] Comparison of nano-and micro-sized particles by three different route administration using a medium-term liver carcinogenesis bioassay in F344 rats (2009)
  • Author(s): 橋本希
  • Organizer: 2009 American Association for Cancer Research Annual Meeting
  • Place of Presentation: Colorado Convention Center, (米国)
  • Year and Date: 2009-04-19
• [Presentation] Comparison of nano-and micro-sized particles by three different route administrations using a medium-term liver carcinogenesis bioassay in F344 rats. (2009)
  • Author(s): 橋本 希
  • Organizer: 2009 American Association for Cancer Research Annual Meeting.
  • Place of Presentation: Colorado Convention Center, Denver, Colorado. U. S. A
  • Year and Date: 2009-04-19
• [Presentation] 気管内投与によるCuOナノサイズ粒子の急性変化の検討-マイクロサイズ粒子との比較による- (2009)
  • Author(s): 橋本希、横平正直、今井田克己, 他
  • Organizer: 第25回日本毒性病理学会
  • Place of Presentation: 浜松市
• [Presentation] 気管内投与によるCuOナノサイズ粒子の急性変化の検討-マイクロサイズ粒子との比較による- (2009)
  • Author(s): 橋本希, 横平正直, 今井田克己, 他
  • Organizer: 第25回日本毒性病理学会
• [Presentation] Comparison of nano- and micro-sized particles by three different route administrations using a medium-term liver carcinogenesis bioassay in F344 rats (2009)
  • Author(s): Hashimoto N, Yokohira M, Imaida K, et al.
  • Organizer: American Association for Cancer Resaech 100^<th> Annual Meeting 2009
• [Presentation] Intratracheal instillation of CuO nanoparticles promotes liver carcinogenesis in F344 rats. (2008)
  • Author(s): 橋本希, 横平正直, 今井田克己, et al.
  • Organizer: 67^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 名古屋
• [Presentation] Intratracheal instillation of CuO nanoparticles promotes liver carcinogenesis in F344 rats (2008)
  • Author(s): Hashimoto N, Yokohira M, Imaida K, et al.
  • Organizer: 67^<th> Annual Meeting of the Japanese Cancer Association
• [Presentation] Establishment of a bioassay for lung carcinogenesis due to fine particlesinstilled intratracheally in F344 rats (2007)
  • Author(s): Yokohira M, Kuno T, Saoo K, Yamakawa K, Suzuki S, Hosokawa K, Matsuda Y, Kinouchi S, Imaida K
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] Detection of epidermal growth factor receptor(EGFR)gene mutation in rat lung tumors induced by X-ray irradiation (2007)
  • Author(s): Kitahashi T, Takahashi M, Tutsumi M, Kusuoka O, Yokohira M Imaida K, Takasuka N, Sugimura T, Wakabayashi K
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] Modulation effect of NNK-induced lung tumor by CYP2A inhibitor,8-MOP administered during promotion or progression phase (2007)
  • Author(s): Kuno T, Saoo K, Yokohira M, Yamakawa K, Hashimoto N, Hosokawa K. Matsuda Y. Imaida K
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] Short-term effect of various chemicals on NNK-induced tumorigenesis in A/J female mouse (2007)
  • Author(s): Matsuda Y, Yamakawa K, Saoo K, Yokohira M, Hosokawa K, Kuno T, Naito Z, Imaida, K.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] A study on the threshold for MeIQx carcinogenesis in lung using A/J mice (2007)
  • Author(s): Suzuki S, Yokohira M, Kuno T, Yamakawa K, Hosokawa K, Matsuda Y, Shiooka T, Imaida, K.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] Potential of inhibitory effects by D-allose, a rare sugar, on liver carcinogenesis in a rat medium-term bioassay (2007)
  • Author(s): Yamakawa K, Yokohira M, Kuno T, Matsuda Y, Hashimoto N, Hosokawa K, Saoo K, Imaida K.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] Enzymatically modified isogercitrin and isoquercitorin, in a rat medium-term liver carcinogenesis bioassay (2007)
  • Author(s): Hosokawa K, Yokohira M, Yamakawa K, Saoo K, Matsuda Y, Suzuki S, Kuno T, Imaida K.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Presentation] Expression of p27 and Skp2 predicts postoperative survival for patients with intrahepatic (2007)
  • Author(s): Hashimoto N, Yachida S, Okano K, Wakabayashi H, Imaida K, Suzuki Y
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-03
• [Book] 第2部社会問題となった疾患と病理学〈環境〉(4.内分泌撹乱化学物質(環境ホルモン)病理と臨床 臨時増刊号)(深山正久, 樋野興夫, 坂元亨宇, 中山淳, 羽場礼次(編集) (2009)
  • Author(s): 今井田克己
  • Publisher: 文光堂
• [Remarks] ホームページ等
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