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Studies on the epigenetic mechanism of arsenic carcinogenesis on human liver cancer cell line

Research Project

Project/Area Number 23790680
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hygiene
Research InstitutionNational Institute for Environmental Studies

Principal Investigator

SUZUKI Takehiro  独立行政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) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsヒ素 / エピジェネティクス / ヒストン修飾 / P16INK4a
Research Abstract

In this study, we investigated the mechanism involved in arsenic-induced carcinogenesis focusing on epigenetic regulations of the tumor suppressor gene p16^<1NK4a> in human urothelial cell lines. The results showed that arsenic exposure induced a significant decrease in expression of p16^<1NK4a> associated with an increase in the level of trimethylated histone H3 lysine 27 (H3K27), a transcription-suppressive histone modification, in the promoter region. The results also showed that arsenic exposure induced a significant increase in expression of H3K27 histone methyltransferase EZH2. These results suggested that the decreased expression of p16^<1NK4a> through histone modification is associated with arsenic-induced carcinogenesis in human urothelial cell lines.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (11 results)

  • [Journal Article] Long-term arsenic exposure induces histone H3 Lys9 dimethylation without altering DNA methylation in the promoter region of p16INK4a and down-regulates its expression in the liver of mice.2013

    • Author(s)
      T. Suzuki and K. Nohara
    • Journal Title

      J. Appl. Toxicol.

      Volume: 33 Issue: 9 Pages: 951-958

    • DOI

      10.1002/jat.2765

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Late-onset increases in oxidative stress and other tumorigenic activities and tumors with a Ha-ras mutation in the liver of adult male C3H mice gestationally exposed to arsenic.2012

    • Author(s)
      Keiko Nohara
    • Journal Title

      Toxicological Science

      Volume: 129 Issue: 2 Pages: 293-304

    • DOI

      10.1093/toxsci/kfs203

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork2012

    • Author(s)
      Maekawa F, Shimba S, Takumi S, Sano T, Suzuki T, Bao J, Ohwada M, Ehara T, Ogawa Y, Nohara K.
    • Journal Title

      Epigenetics

      Volume: 7 (9) Pages: 1046-56

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork2012

    • Author(s)
      Maekawa F., Shimba S., Takumi S., Sano T., Suzuki T., Bao J., Ohwada M., Ehara T., Ogawa Y., Nohara K.
    • Journal Title

      Epigenetics

      Volume: 7 Pages: 1046-1056

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Fosb遺伝子発現調節における遺伝子領域内部DNAメチル化の関与の検討2013

    • Author(s)
      鈴木武博,野原恵子
    • Organizer
      第83回日本衛生学会学術総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 無機ヒ素の胎児期曝露による後発的発癌増加の機序2013

    • Author(s)
      野原恵子,鈴木武博,岡村和幸,内匠正太
    • Organizer
      第83回日本衛生学会学術総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 胎児期ヒ素曝露によるC3Hマウス雄肝臓での脂質代謝変化とHa-ras変異をもった腫瘍の増加2012

    • Author(s)
      野原恵子,鈴木武博,岡村和幸,内匠正太,前川文彦,小堀真珠子
    • Organizer
      第1回日本DOHaD研究会年会
    • Place of Presentation
      東京
    • Year and Date
      2012-08-04
    • Related Report
      2012 Final Research Report
  • [Presentation] 無機ヒ素による発がんへの変異とエビ変異の関与2012

    • Author(s)
      野原恵子,鈴木武博,岡村和幸,内匠正太,
    • Organizer
      環境エピゲノミクス研究会第7回定例会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-12
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒ素によるマウス肝癌の網羅的DNAメチル化解析による領域特異的メチル化変化とFosb発現増加の検出2012

    • Author(s)
      鈴木武博,山下聡,内匠正太,立石幸代,佐野友春,牛島俊和,野原恵子
    • Organizer
      第6回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] gpt deltaマウスを用いた無機ヒ素によるinvivo突然変異解析2012

    • Author(s)
      内匠正太,青木康展,佐野友春,鈴木武博,能美健彦,野原恵子
    • Organizer
      日本環境変異原学会第41回大会
    • Place of Presentation
      静岡
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒ素によるFosb発現増加に関与するエピジェネティック修飾の検討2012

    • Author(s)
      鈴木武博,野原恵子
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] C3Hマウスへの胎児期無機ヒ素曝露によるF1およびF2世代でのHa-ras変異をもった腫瘍の増加2012

    • Author(s)
      野原恵子,岡村和幸,鈴木武博,村井景,新城恵子,近藤豊
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] gpt deltaマウスを用いた無機ヒ素によるin vivo突然変異解析2012

    • Author(s)
      内匠正太, 青木康展, 佐野友春, 鈴木武博, 能美健彦, 野原恵子
    • Organizer
      日本環境変異原学会第41回大会
    • Place of Presentation
      静岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 無機ヒ素による発がんへの変異とエピ変異の関与

    • Author(s)
      野原恵子, 鈴木武博, 岡村和幸, 内匠正太
    • Organizer
      環境エピゲノミクス研究会第7回定例会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] 胎児期ヒ素曝露によるC3Hマウス雄肝臓での脂質代謝変化とHa-ras変異をもった腫瘍の増加

    • Author(s)
      野原恵子, 鈴木武博, 岡村和幸, 内匠正太, 前川文彦, 小堀真珠子
    • Organizer
      第1回日本DOHaD研究会年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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