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Studies on the regulation of Fos family gene expression involved in late-onset increases of tumor induced by arsenic

Research Project

Project/Area Number 25460831
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hygiene and public health
Research InstitutionNational Institute for Environmental Studies

Principal Investigator

Suzuki Takehiro  国立研究開発法人国立環境研究所, 環境健康研究センター, 主任研究員 (60425494)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsヒ素 / エピジェネティクス / Fosb
Outline of Final Research Achievements

In this study, we investigated the mechanisms of Fosb gene expression focused on epigenetic regulation by arsenic in mouse hepatoma Hepa1c1c7 cells. Upon exposure of Hepa1c1c7 cells to 0.5 μM As2O3, the expression of Fosb was greatly increased after 2 days. The bisulfite sequencing revealed that DNA methylation level decreased in the DNA regions around transcription start sites (TSS) of Fosb gene by arsenic. We also found a decrease of DNA methylation level in the same DNA region and an increase of Fosb gene expression by DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine and siDnmt3b in Hepa1c1c7 cells. These results suggested that the DNA methylation change in the DNA regions around TSS of Fosb gene by Dnmt3b is involved in its expression regulation by arsenic in Hepa1c1c7 cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (26 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Invited: 2 results) Book (1 results)

  • [Journal Article] Augmenting effects of gestational arsenite exposure of C3H mice on the hepatic tumors of the F2 male offspring via the F1 male offspring2015

    • Author(s)
      Nohara K, Okamura K, Suzuki T, Murai H, Ito T, Shinjo K, Takumi S, Michikawa T, Kondo Y, Hata K.
    • Journal Title

      J Appl Toxicol

      Volume: 印刷中 Issue: 1 Pages: 105-112

    • DOI

      10.1002/jat.3149

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 無機ヒ素によるマウス肝がん増加に関連したエピジェネティック変化とDNAメチル化マーカーの探索2015

    • Author(s)
      鈴木武博, 野原恵子
    • Journal Title

      日本衛生学雑誌

      Volume: 印刷中

    • NAID

      130005098972

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 妊娠期無機ヒ素曝露による子での癌遺伝子体細胞突然変異を介した発癌増加と多世代・継世代影響2014

    • Author(s)
      野原恵子, 鈴木武博, 内匠正太, 岡村和幸
    • Journal Title

      日本衛生学雑誌

      Volume: 69 Pages: 92-96

    • NAID

      130004512932

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] in vivo mutagenicity of arsenite in the livers of gpt delta transgenic mice2014

    • Author(s)
      S. Takumi, Y. Aoki, T. Sano, T. Suzuki, T. Nohmi and K. Nohara
    • Journal Title

      Mutat. Res.

      Volume: 760 Pages: 42-47

    • DOI

      10.1016/j.mrgentox.2013.12.001

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genome-wide analysis of DNA methylation changes induced by gestational arsenic exposure in liver tumors2013

    • Author(s)
      T. Suzuki et al.
    • Journal Title

      Cancer Sci.

      Volume: 104 Issue: 12 Pages: 1575-1585

    • DOI

      10.1111/cas.12298

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Fosb発現とDNAメチル化変化の対応関係を検討する実験系の探索2015

    • Author(s)
      鈴木武博・岡村和幸・野原恵子
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      九州大学(福岡)
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 無機ヒ素のエピジェネティック作用、変異原性、多世代・継世代影響2015

    • Author(s)
      野原恵子, 鈴木武博, 岡村和幸, 内匠正太
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      九州大学(福岡)
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] バングラデシュ住民の慢性的ヒ素曝露と血液ゲノムにおけるDNAメチル化に関する検討2015

    • Author(s)
      鈴木武博, Khaled Hossain, 姫野誠一郎, 野原恵子
    • Organizer
      第21回ヒ素シンポジウム
    • Place of Presentation
      徳島文理大学(徳島)
    • Year and Date
      2015-11-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] Gestational arsenic exposure affects gene expression in the kidney and lung in the F1 and F2 mice2015

    • Author(s)
      S. Takumi, K. Okamura, T. Suzuki, H. Hano, K. Nohara, H. Yanagisawa
    • Organizer
      Society of Toxicology 54th Annual Meeting
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2015-03-22 – 2015-03-26
    • Related Report
      2014 Research-status Report
  • [Presentation] The effects of gestational arsenite exposure on the F2 generation: Role of epigenetics2015

    • Author(s)
      K. Nohara, K. Okamura, T. Suzuki, I. Hatada, K. Hata
    • Organizer
      Society of Toxicology 54th Annual Meeting
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2015-03-22 – 2015-03-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Search for the signaling pathways involved in the hepatic tumor increase in the F2 male C3H mice born to gestationally arsenite-exposed F0 females2014

    • Author(s)
      K. Nohara , K. Okamura , T. Suzuki, H. Murai, M. Kobori
    • Organizer
      Prenatal Programming and Toxicity(PPTOX)IV Meeting
    • Place of Presentation
      Boston (USA)
    • Year and Date
      2014-10-26 – 2014-10-29
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス肝臓癌細胞株における無機ヒ素によるFosbの発現とDNAメチル化変化2014

    • Author(s)
      鈴木武博, 野原恵子
    • Organizer
      フォーラム2014 衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 妊娠期無機ヒ素曝露によるF2雄マウスでの肝腫瘍増加の機序の探索2014

    • Author(s)
      野原恵子、岡村和幸、鈴木武博、村井景、小堀真珠子
    • Organizer
      フォーラム2014 衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] C3Hマウス胎児期ヒ素曝露が次世代に及ぼす影響2014

    • Author(s)
      内匠正太, 岡村和幸, 鈴木武博, 羽野寛, 野原恵子, 柳澤裕之
    • Organizer
      第25回日本微量元素学会学術集会
    • Place of Presentation
      岡山大学創立五十周年記念館(岡山県岡山市)
    • Year and Date
      2014-07-03 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] C3Hマウスへの無機ヒ素妊娠期曝露はF1雄を介してF2雄の肝癌を増加させる2014

    • Author(s)
      野原恵子、鈴木武博、岡村和幸、村井景、上田佳代
    • Organizer
      第41回日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 胎児期無機ヒ素曝露によるマウス肝腫瘍のDNAメチル化変化2014

    • Author(s)
      鈴木武博, 山下聡, 牛島俊和, 内匠正太, 佐野友春, 野原恵子
    • Organizer
      第84回日本衛生学会学術総会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2014-05-25 – 2014-05-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 胎児期ヒ素曝露が標的臓器に及ぼす影響2014

    • Author(s)
      内匠正太, 岡村和幸, 鈴木武博, 羽野寛, 野原恵子, 柳澤裕之
    • Organizer
      第84回日本衛生学会学術総会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2014-05-25 – 2014-05-27
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス肝癌細胞株におけるFosb発現とDNAメチル化の関連2014

    • Author(s)
      鈴木武博, 野原恵子
    • Organizer
      分子予防環境医学研究会第13回大会
    • Place of Presentation
      和歌山
    • Related Report
      2013 Research-status Report
  • [Presentation] 胎児期ヒ素曝露により後発的に増加する肝腫瘍における遺伝子発現変化の探索2014

    • Author(s)
      岡村和幸, 鈴木武博, 村井景, 野原恵子
    • Organizer
      分子予防環境医学研究会第13回大会
    • Place of Presentation
      和歌山
    • Related Report
      2013 Research-status Report
  • [Presentation] Identification of DNA methylation changes in the liver tumors induced by gestational arsenic exposure using genome-wide analysis2014

    • Author(s)
      Suzuki T., Yamashita S., Ushijima T., Takumi S., Sano T., Nohara K.
    • Organizer
      Society of Toxicology 53rd Annual Meeting
    • Place of Presentation
      アメリカ フェニックス
    • Related Report
      2013 Research-status Report
  • [Presentation] Maternal arsenic exposure of C3H mice increases hepatic tumor with an activating mutation in the oncogene Ha-ras in the F2 generation2014

    • Author(s)
      Nohara K., Okamura K., Suzuki T., Murai H., Ito T., Shinjo K., Kondo Y.
    • Organizer
      Society of Toxicology 53rd Annual Meeting
    • Place of Presentation
      アメリカ フェニックス
    • Related Report
      2013 Research-status Report
  • [Presentation] In vivo mutagenicity assay of arsenite using gpt delta transgenic mice2014

    • Author(s)
      Takumi S., Aoki Y., Sano T., Suzuki T., Nohmi T., and Nohara K.
    • Organizer
      Society of Toxicology 53rd Annual Meeting
    • Place of Presentation
      アメリカ フェニックス
    • Related Report
      2013 Research-status Report
  • [Presentation] 胎児期無機ヒ素曝露によるマウス肝腫瘍のDNAメチル化変化2014

    • Author(s)
      鈴木武博, 山下聡, 牛島俊和, 内匠正太, 佐野友春, 野原恵子
    • Organizer
      第84回日本衛生学会学術総会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] マウス胎児期無機ヒ素曝露によってF2世代の肝臓において誘導される遺伝子発現変化2013

    • Author(s)
      野原恵子、岡村和幸、鈴木武博、村井景、内匠正太、新城恵子、近藤豊
    • Organizer
      第7回日本エピジェネティクス研究会年会
    • Place of Presentation
      奈良
    • Related Report
      2013 Research-status Report
  • [Presentation] 胎児期ヒ素曝露によるマウス肝腫瘍の領域特異的なDNAメチル化と遺伝子発現変化2013

    • Author(s)
      鈴木武博, 山下聡, 牛島俊和, 内匠正太, 佐野友春, 野原恵子
    • Organizer
      日本DOHaD研究会第2回学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] 毒性の科学2014

    • Author(s)
      鈴木武博, 野原恵子
    • Total Pages
      200
    • Publisher
      東大出版会
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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