ヒ素曝露の健康影響評価とその感受性因子の探索

• Project/Area Number: 23810023
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Ehime University
• Principal Investigator: 阿草 哲郎 愛媛大学, 学内共同利用施設等, その他 (50403853)
• Project Period (FY): 2011-08-24 – 2013-03-31
• Project Status: Declined (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ヒ素 / 遺伝子多型 / 遺伝子発現量 / アジア / 環境化学 / 環境毒性学 / リスク評価 / 国際共同研究

Research Abstract

本申請課題は、環境要因(ヒ素曝露)と遺伝要因(遺伝子多型)の双方を考慮しながら無機ヒ素の健康リスクを評価し、その感受性に寄与する要因(ハイリスクファクター)を同定することを最終目的とする。
本年度は、無機ヒ素の毒性影響に大きく関係している無機ヒ素代謝能力の感受性について精査した。体内に取り込まれた無機ヒ素は、arsenic (+30xidation state) methyl transferase (AS3MT)という酵素によってメチル化され、尿中へ排泄される。既存の研究において、無機ヒ素代謝能力が低いほど、無機ヒ素曝露によるがん等の影響が出やすいことが報告されていることから、無機ヒ素代謝能力の感受性に着目することは重要である。しかしながら、これまで無機ヒ素汚染地域の住民を対象にAS3MTの発現量と無機ヒ素代謝能力の関係を調査した研究は無い。本研究では、ベトナムの無機ヒ素汚染地域の住民を対象に尿中ヒ素化合物を分析し、そのヒ素化合物組成から推定したヒ素代謝能力と血中AS3MTmRNA発現量の関連について解析した。
2006年3月および2007年9月に、ベトナム北部のHoa Hau、Liem Thuan、Thanh VanhとThach Hoaで、地下水(n=64)と住民の尿(n=190)、血液(n=190)を採取した。総ヒ素をICP-MSで、各ヒ素化合物(arsenite(As[III]),arsenate(As[V]),monomethylarsonic(MMA),dimethylarsinicacid(DMA),arsenobetaine(AB))をHPLC/ICP-MSで定量した。血中AS3MT mRNAの発現量は、total RNAを抽出した後、リアルタイムPCRにより定量した。
分析の結果、地下水中ヒ素濃度は<0.1-502μg/lであり、一部の地下水からWHOの飲料水の安全基準値(10μg/l)を超える濃度のヒ素が検出された。飲用水中総ヒ素濃度とヒト尿中DMA、MMA、As[III]濃度の間に有意な正の相関関係がみられたことから、地域住民は地下水を経由してヒ素に曝露していることが示唆された。血中AS3MT mRNA発現量と尿中総ヒ素濃度に対するDMA濃度の割合の間に有意な正の相関関係が認められた。このことから、無機ヒ素のメチル化はAS3MTの発現量に依存すると推察された。

Research Products

• [Journal Article] Individual variations in arsenic metabolism in Vietnamese : the association with arsenic exposure and GSTP1 genetic polymorphism (2012)
  • Author(s): Agusa, T.
  • Journal Title: Metallomics : Integrated Biometal Science Volume: 4(1) Issue: 1 Pages: 91-100
  • DOI: 10.1039/c1mt00133g
  • Peer Reviewed
• [Journal Article] Multi-trace element levels and arsenic speciation in urine of e-waste recycling workers from Agbogbloshie, Accra in Ghana (2012)
  • Author(s): Asante, K. A.
  • Journal Title: Science of the Total Environment Volume: 424 Pages: 63-73
  • DOI: 10.1016/j.scitotenv.2012.02.072
  • Peer Reviewed
• [Journal Article] Genetic variation of FUT2 in a Vietnamese population: Identification of two novel Se enzyme - Inactivating mutations (2012)
  • Author(s): Soejima, M.
  • Journal Title: Transfusion Volume: 52(6) Issue: 6 Pages: 1268-1275
  • DOI: 10.1111/j.1537-2995.2011.03485.x
  • Peer Reviewed
• [Journal Article] Impact of Metals in Surface Matrices from Formal and Informal Electronic-waste Recycling Around Metro Manila, the Philippines, and intra-Asian Comparison. (2012)
  • Author(s): Akifumi Eeuchi
  • Journal Title: Journal of Hazardous Materials Volume: 221-222 Pages: 139-146
  • DOI: 10.1016/j.jhazmat.2012.04.019
  • Peer Reviewed
• [Journal Article] Intake and excretion of arsenicals in green (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) (2011)
  • Author(s): Agusa, T.
  • Journal Title: Environmental Chemistry Volume: 8(1) Issue: 1 Pages: 19-29
  • DOI: 10.1071/en10091
  • Peer Reviewed
• [Journal Article] Stable isotope-guided analysis of biomagnification profiles of arsenic species in a tropical mangrove ecosystem (2011)
  • Author(s): Tu, N.P.C., Agusa, T., Ha, N.N., Tuyen, B.C., Tanabe, S., Takeuchi, I.
  • Journal Title: Marine Pollution Bulletin Volume: 63 Issue: 5-12 Pages: 124-134
  • DOI: 10.1016/j.marpolbul.2011.03.002
  • Peer Reviewed
• [Journal Article] Accumulation of trace elements in harp seals (Phoca groenlandica) from Pangnirtung in the Baffin Island, Canada (2011)
  • Author(s): Agusa, T.
  • Journal Title: Marine Pollution Bulletin Volume: 63(5-12) Issue: 5-12 Pages: 489-499
  • DOI: 10.1016/j.marpolbul.2011.02.022
  • Peer Reviewed
• [Journal Article] 8-Hydroxy-2’-deoxyguanosine and arsenic compounds in urine and serum of a 4-year-old child suffering from acute promyelocytic leukemia during treatment with arsenic trioxide (2011)
  • Author(s): Fujihara, J.
  • Journal Title: Forensic Toxicology Volume: 29(1) Issue: 1 Pages: 65-68
  • DOI: 10.1007/s11419-010-0104-z
  • Peer Reviewed
• [Journal Article] Spatial distribution and corresponding determining factors of metal concentrations in surface sediments of Beppu Bay, southwest Japan (2011)
  • Author(s): Amano, A
  • Journal Title: Marine Environmental Research Volume: 71(4) Issue: 4 Pages: 247-256
  • DOI: 10.1016/j.marenvres.2011.01.009
  • Peer Reviewed
• [Journal Article] Accumulation features of trace elements in mass-stranded harbor seals (Phoca vitulina) in the North Sea coast in 2002: The body distribution and association with growth and nutrition status (2011)
  • Author(s): Agusa, T.
  • Journal Title: Marine Pollution Bulletin Volume: 62(5) Issue: 5 Pages: 963-975
  • DOI: 10.1016/j.marpolbul.2011.02.047
  • Peer Reviewed
• [Journal Article] Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphism (2011)
  • Author(s): Agusa, T.
  • Journal Title: International Journal of Molecular Sciences Volume: 12(4) Issue: 4 Pages: 2351-2382
  • DOI: 10.3390/ijms12042351
  • Peer Reviewed
• [Journal Article] Arsenic and Mn levels in Isaza (Gymnogobius isaza) during the mass mortality event in Lake Biwa, Jspan (2011)
  • Author(s): Sawako Horai Hirata, Daisuke Hayase, Akifumi Eguchi, Takaaki Itai, Kei Nomiyama, Tomohiko Isobe, Tetsuro Agusa, Toshiyuki Ishikawa, Michio Kumagai, Shinsuke Tanabe
  • Journal Title: Environmental Pollution Volume: 159 Issue: 10 Pages: 2789-2796
  • DOI: 10.1016/j.envpol.2011.05.007
  • Peer Reviewed
• [Journal Article] Trace elements in Anadara spp.(Mollusca : Bivalva) collected along the coast of Vietnam, with emphasis on regional differences and human health risk assessment (2011)
  • Author(s): Tu, N.P.C., Ha, N.N., Agusa, T., Ikemoto, T., Tuyen, B.C., Tanabe, S., Takeuchi, I.
  • Journal Title: Fisheries Science Volume: 77 Issue: 6 Pages: 1033-1043
  • DOI: 10.1007/s12562-011-0410-3
  • NAID: 10029654844
  • Peer Reviewed
• [Presentation] Gene loci associated with metabolism of inorganic arsenic in mice (2012)
  • Author(s): Agusa, T., Komori, H., Soga, Y., Nose, M., Mori, S., Kubota, R., Tanabe, S., Iwata, H.
  • Organizer: The Society of Toxicology (SOT) 51st Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-03-12
• [Presentation] Contamination by trace elements in e-waste recycling workers in the Philippines (2012)
  • Author(s): Agusa, T., Takigami, H., Eguchi, A., Fujimori, T., Bekki, K., Yoshida, A., Terazono, A., Ballesteros Jr., F.C., Takahashi, S., Iwata, H., Tanabe, S.
  • Organizer: The 8th NIES Workshop on E-Waste
  • Place of Presentation: Quezon, Philippines(招待講演)
  • Year and Date: 2012-01-24
• [Presentation] 組換え近交系マウスを用いたヒ素代謝感受性規定因子の探索 (2011)
  • Author(s): 阿草哲郎, 小森浩章, 曽我美子, 能勢属人, 森士朗, 久保田領志, 田辺信介, 岩田久人
  • Organizer: 第17回ヒ素シンポジウム
  • Place of Presentation: つくば(奨励賞受賞)
  • Year and Date: 2011-11-20
• [Presentation] Metallomics of wildlife : an approach to understand the mechanism of mercury detoxification (2011)
  • Author(s): Agusa, T., Ikemoto, T., Kunito, T., Yasugi, S., Tanabe S., Iwata H
  • Organizer: SETAC (Society of Environmental Toxicology and Chemistry) North America 32nd Annual Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2011-11-17
• [Presentation] フィリピンのe-wasteリサイクル労働者における微量元素曝露の実態 (2011)
  • Author(s): 阿草哲郎, 滝上英孝, 江口哲史, 藤森崇, 戸次加奈江, 吉田綾, 寺園淳, Florencio C.Ballesteros Jr., 高橋真, 岩田久人, 田辺信介
  • Organizer: 第22回廃棄物資源循環学会研究発表会
  • Place of Presentation: 東京都文京区
  • Year and Date: 2011-11-04
• [Presentation] Human exposure to trace elements from e-waste recycling sites in the Philippines (2011)
  • Author(s): Agusa, T., Takigami, H., Eguchi, A., Fujimori, T., Bekki, K., Yoshida, A., Terazono, A., Ballesteros Jr., F.C., Takahashi, S., Iwata, H., Tanabe, S.
  • Organizer: The Life Cycle of Metals : Improving Health, Environment and Human Security
  • Place of Presentation: Bunkyo-ku, Tokyo(招待講演)
  • Year and Date: 2011-11-01
• [Presentation] Metabolism of As in residents from the areas with As-contaminated groundwater, Vietnam : effects of As exposure levels and genetic polymorphisms (2011)
  • Author(s): Agusa, T., Kunito, T., Tue, N.M., Lan, V.T.M., Fujihara, J., Takeshita, H., Minh, T.B., Trang, P.T.K., Takahashi, S., Viet, P.H., Tanabe, S., Iwata, H.
  • Organizer: IX International Society of Trace Element Research in Humans (ISTERH)
  • Place of Presentation: Antalya, Turkey(招待講演)
  • Year and Date: 2011-10-19
• [Presentation] Contamination by trace elements in e-waste recycling workers from Accra in Ghana (2011)
  • Author(s): Asante, K.W., Agusa, T., Biney, C.A., Dapaah-Siakwan, S., Bello, M., Takahashi, S., Tanabe, S.
  • Organizer: IX International Society of Trace Element Research in Humans (ISTERH)
  • Place of Presentation: Antalya, Turkey
  • Year and Date: 2011-10-19
• [Presentation] Exposure, metabolism, and toxic effect of arsenic in residents from arsenic-contaminated groundwater areas of southeast Asia (2011)
  • Author(s): Agusa, T., Kunito, T., Inoue, S., Kubota, R., Ramu, K., Minh, T.B., Tue, N.M., Ha, N.N., Tu, N.P.C., Fujihara, J., Charaborty, P., Chamnan, C., Trang, P.T.K., Reungsang, A., Srisuk, K., Nakamura, S., Takizawa, S., Takeshita, H., Takahashi, S., Subramanian, A., Tuyen, B.C., Viet, P.H., Tana, T.S., Tanabe, S., Iwata, H.
  • Organizer: International Symposium on Advanced studies by Young Scientists on Environmental Pollution and Ecotoxicology
  • Place of Presentation: Matsuyama, Japan
  • Year and Date: 2011-08-05
• [Presentation] ベトナム人におけるヒ素曝露量と代謝遺伝子発現量の関係 (2011)
  • Author(s): 阿草哲郎、國頭恭、Nguyen Minh Tue、Vi Thi Mai Lan、Tu Binh Minh、Pham Thi Kim Trang、高橋真、Pham Hung Viet、田辺信介、岩田久人
  • Organizer: 第20回環境化学討論会
  • Place of Presentation: 熊本
  • Year and Date: 2011-07-17
• [Presentation] ベトナムバッテリー処理施設における鉛暴露の実態と健康リスク評価 (2011)
  • Author(s): 野口貴子, 板井啓明, Nguyen Minh Tue, 阿草哲郎, 平田(宝来)佐和子, Pham Thi Kim Trang, Pham Hung Viet, 高橋真, 田辺信介
  • Organizer: 第20回環境化学討論会
  • Place of Presentation: 熊本
  • Year and Date: 2011-07-17
• [Presentation] フィリピンのe-wasteリサイクル労働者における微量元素汚染 (2011)
  • Author(s): 阿草哲郎, 滝上英孝, 江口哲史, 藤森崇, 戸次加奈江, 吉田綾, 寺園淳, Florencio C.Ballesteros Jr., 高橋真, 田辺信介
  • Organizer: 第20回環境化学討論会
  • Place of Presentation: 熊本
  • Year and Date: 2011-07-16
• [Presentation] ベトナム鉛バッテリーリサイクル地域住民の暴露実態と健康影響評価 (2011)
  • Author(s): 藤森崇, 滝上英孝, 阿草哲郎, 江口哲史, 戸次加奈江, 吉田綾, 寺園淳, Florencio C.Ballesteros Jr.
  • Organizer: 第20回環境化学討論会
  • Place of Presentation: 熊本
  • Year and Date: 2011-07-16
• [Presentation] ベトナム人におけるヒ素代謝能力とAS3MT遺伝子発現量の関係 (2011)
  • Author(s): 阿草哲郎、國頭恭、Nguyen Minh Tue、Vi Thi Mai Lan、Tu Binh Minh、Pham Thi Kim Trang、高橋真、Pham Hung Viet、田辺信介、岩田久人
  • Organizer: 第22回日本微量元素学会
  • Place of Presentation: 京都
  • Year and Date: 2011-07-01
• [Presentation] Individual variations in arsenic metabolism in Vietnamese : the association with arsenic exposure and GSTP1 genetic polymorphisms (2011)
  • Author(s): Agusa, T., Kunito, T., Tue, N.N., Lan, V.T.M., Fujihara, J., Takeshita, H., Minh, T.B., Trang, P.T.K., Takahashi, S., Viet, P.H., Tanabe, S., Iwata, H.
  • Organizer: 3rd International Symposium on Metallomics
  • Place of Presentation: Munster, Germany
  • Year and Date: 2011-06-17
• [Book] Interdisciplinary Studies on Environmental Chemistry Vol.6 Advanced Environmental studies by Young Scientists (2012)
  • Author(s): Agusa, T., Kunito, T., Kubota, R., Tanabe, S., Iwata, H.
  • Publisher: TERRAPUB
• [Remarks]
  • URL: http://resarchmap.jp/read0097650/?lang=japanese