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Prevention of benzene (or radiation) induced acute myeloid leukemia (or bone marrow failure) by myeloperoxidase inhibitor

Research Project

Project/Area Number 24790602
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hygiene
Research InstitutionKagoshima University

Principal Investigator

NISHIKAWA Takuro  鹿児島大学, 医学部・歯学部附属病院, 助教 (90535725)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsベンゼン / 発がん / ミエロペルオキシダーゼ / 活性酸素 / マイクロアレイ / 急性骨髄性白血病
Research Abstract

While it is known that benzene induces myeloid leukemia in humans, the mechanism has yet to be clarified. Previously, we suggested that myeloperoxidase (MPO) was the key enzyme because it promotes generation of powerful oxidant hypochlorous acid which reacting with DNA. In our study, using a whole-human-genome oligonucleotide microarray, we analyzed the genome-wide expression profiles of HL60 human promyelocytic cell lines exposed to 1,2,4-benzenetriol (BT) with or without MPO inhibition. The microarray analysis revealed that 4h exposure to BT changed the expressionin HL60 cells of 1213 genes associated with transcription, RNA metabolic processes, immuneresponse, apoptosis, cell death, and biosynthetic processes, and that these changes were dramatically lessened by MPO-specific inhibition. Gene expression profiles along with GO and KEGG pathway annotation analysis suggest that there maybe a role for MPO as an examination marker or in prophylaxis forchemical carcinogenesis.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (11 results)

  • [Journal Article] Effect of myeloperoxidase inhibition on gene expression profiles in HL-60 cells exposed to 1, 2, 4,-benzenetriol.2014

    • Author(s)
      Miyahara E, Nishikawa T, Takeuchi T, Yasuda K, Okamoto Y, Kawano Y, Horiuchi M.
    • Journal Title

      Toxicology

      Volume: 317 Pages: 50-57

    • DOI

      10.1016/j.tox.2014.01.007

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Outcomes of immunological interventions for mixed chimerism following allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia2013

    • Author(s)
      Inagaki J, Fukano R, Nishikawa T, Nakashima K, Sawa D, Ito N, Okamura J
    • Journal Title

      Pediatr Blood Cancer

      Volume: 60 Issue: 1 Pages: 116-120

    • DOI

      10.1002/pbc.24259

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ramsay Hunt syndrome in a girl with acute lymphoblastic leukemia during maintenance therapy2013

    • Author(s)
      Kodama Y, Okamoto Y, Nishi J, Hashiguchi S, Yamaki Y, Kurauchi K, Tanabe T, Shinkoda Y, Nishikawa T, Suda Y, Kawano Y
    • Journal Title

      J Pediatr Hematol Oncol

      Volume: 35 Issue: 5 Pages: 224-225

    • DOI

      10.1097/mph.0b013e3182830d30

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent pulmonary edema after umbilical cord blood transplantation in a patient with infant acute lymphoblastic leukemia2013

    • Author(s)
      Sawa D, Nishikawa T, Nakashima K, Morita H, Ito N, Fukano R, Okamura J, Inagaki J
    • Journal Title

      Rinsho Ketsueki

      Volume: 54(3) Pages: 273-278

    • NAID

      10031165615

    • URL

      https://www.jstage.jst.go.jp/article/rinketsu/54/3/54_273/_article

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent pulmonary edema after umbilical cord blood transplantation in a patient with infant acute lymphoblastic leukemia.2013

    • Author(s)
      Sawa D, Nishikawa T, Nakashima K, Morita H, Ito N, Fukano R, Okamura J, Inagaki J.
    • Journal Title

      Rinsho Ketsueki.

      Volume: 54(3) Pages: 273-278

    • NAID

      10031165615

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ramsay Hunt Syndrome in a Girl With Acute Lymphoblastic Leukemia During Maintenance Therapy.2013

    • Author(s)
      Kodama Y, Okamoto Y, Nishi J, Hashiguchi S, Yamaki Y, Kurauchi K, Tanabe T, Shinkoda Y, Nishikawa T, Suda Y, Kawano Y.
    • Journal Title

      J Pediatr Hematol Oncol.

      Volume: in print

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The second therapeutic trial for children with hematological malignancies who relapsed after their first allogeneic SCT:long-term outcomes2012

    • Author(s)
      Nishikawa T, Inagaki J, Nagatoshi Y, Fukano R, Nakashima K, Ito N, Sawa D, Kawano Y, Okamura J
    • Journal Title

      Pediatr Transplant

      Volume: 16 Issue: 7 Pages: 722-728

    • DOI

      10.1111/j.1399-3046.2012.01737.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful treatment with plasma exchange for disseminated cidofovir - resistant adenovirus disease in a pediatric SCT recipient2012

    • Author(s)
      Nishikawa T, Nakashima K, Fukano R, Okamura J, Inagaki J
    • Journal Title

      Bone Marrow Transplant

      Volume: 47 Issue: 8 Pages: 1138-1139

    • DOI

      10.1038/bmt.2011.227

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ベンゼン発がんの機構解析2014

    • Author(s)
      西川拓朗、宮原恵弥子、出雲公子、堀内正久、岡本康裕、河合慶親、河野嘉文、竹内亨
    • Organizer
      第84回日本衛生学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Final Research Report
  • [Presentation] Validation of a test dose strategy for administering intravenous busulfan in the setting of pediatric myeloablative stem cell transplantation : Clinical and pharmacokinetic results2014

    • Author(s)
      Nishikawa T, Okamoto Y, Tanabe T, Kurauchi K, Nakagawa S, Abematsu T, Kodama Y, Shinkoda Y, Kawano Y
    • Organizer
      40th Annual Meeting of the European Group for Blood and Marrow Transplantation
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] 静注ブスルファン(ivBu)試験投与を用いた小児ivBu移植前処置の安全性の確立2014

    • Author(s)
      西川拓朗、岡本康裕、倉内宏一郎、田邊貴幸、棈松貴成、中川俊輔、児玉祐一、新小田雄一、河野嘉文
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Final Research Report
  • [Presentation] 静注ブスルファン(ivBu)試験投与を用いた小児ivBu移植前処置の安全性の確立.2014

    • Author(s)
      西川拓朗,岡本康裕,倉内宏一郎,田邊貴幸,棈松貴成,中川俊輔,児玉祐一,新小田 雄一,河野嘉文.
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report
  • [Presentation] Validation of a test dose strategy for administering intravenous busulfan in the setting of pediatric myeloablative stem cell transplantation: Clinical and pharmacokinetic results2014

    • Author(s)
      Nishikawa T, Okamoto Y, Tanabe T, Kurauchi K, Nakagawa S, Abematsu T, Kodama Y, Shinkoda Y, Kawano Y
    • Organizer
      40th Annual Meeting of the EBMT (European Group for Blood and Marrow Transplantation)
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] ベンゼン発がん機構の解析2014

    • Author(s)
      西川拓朗,宮原恵弥子,出雲公子,堀内正久,岡本康裕,河合慶親,河野嘉文,竹内亨
    • Organizer
      第84回日本衛生学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Annual Research Report
  • [Presentation] ブスルファンを前処置として使用した造血細胞移植の検討―血中濃度と移植成績・合併症の関係、経口製剤との比較―2013

    • Author(s)
      西川拓朗、岡本康裕、八牧愉二、倉内宏一郎、田邊貴幸、中川俊輔、児玉祐一、新小田雄一、河野嘉文
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] ALLに対する寛解導入療法中の敗血症発症のリスク因子解析 : KYCCSG ALL96, ALL02研究2012

    • Author(s)
      西川拓朗、岡本康裕、古賀友紀、住江愛子、松崎彰信、大園秀一、上田耕一郎、稲田浩子、稲垣二郎、永利義久、新小田雄一、川上清、野村優子、柳井文男、下之段秀美、盛武浩、中山秀樹、日高靖文、堀田紀子、岡村純、河野嘉文
    • Organizer
      第54回日本小児血液・がん学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Stem cell transplantation for acute leukemia with t2012

    • Author(s)
      Nishikawa T, Kato K, Ito N, Sawa D, Nakashima K, Fukano R, Tsuchida M, Okamura J, Inagaki J
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Stem cell transplantation for acute leukemia with t(10;11)(p12;q14).2012

    • Author(s)
      Nishikawa T, Kato K, Ito N, Sawa D, Nakashima K, Fukano R, Tsuchida M, Okamura J, Inagaki J.
    • Organizer
      第74回日本血液学会学術集会The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] ALLに対する寛解導入療法中の敗血症発症のリスク因子解析:KYCCSG ALL96, ALL02 研究.2012

    • Author(s)
      西川拓朗,岡本康裕,古賀友紀ら
    • Organizer
      第54回日本小児血液・がん学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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