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居住環境中の揮発性有機化合物による免疫毒性および発がん性の分子機構とリスク評価

Research Project

Project/Area Number 15790285
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Hygiene
Research InstitutionMie University

Principal Investigator

平工 雄介  三重大学, 医学部, 助手 (30324510)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords揮発性有機化合物 / エチルベンゼン / 代謝活性化 / DNA損傷 / 発がん性 / 免疫毒性 / 活性酸素 / リスク評価 / 室内汚染物質 / ヘルパーT細胞
Research Abstract

大気中汚染物質の中でも、特に屋内の化学物質による健康障害は緊急に解決されるべき重要な問題である。新築住宅の室内では、建築材料や家具に使用される接着剤や塗装剤などからホルムアルデヒド、ベンゼン、トルエン、キシレン、エチルベンゼンなどの揮発性有機化合物(VOC)が空気中に放出される。ごれらの物質には少量でも長期にわたり連続的に曝露されるため、発がんなどの健康障害が懸念される。エチルベンゼンはラットで腎に、マウスで肺、肝臓に悪性腫瘍を形成するという報告がある。本研究ではVOC、特にエチルベンゼンによる遺伝子損傷機構をヒトがん関連遺伝子DNA断片を用いて解析した。我々はエチルベンゼンを太陽光に曝露した場合に過酸化水素および過酸化物が生成され、銅存在下で酸化的DNA損傷を起こすことを明らかにした(BBRC 2003)。さらに我々は代謝活性化されたエチルベンゼンによるDNA損傷について検討した。エチルベンゼンはラット肝ミクロソームによりベンゼン環の水酸化を受けてエチルハイドロキノンおよび4-エチルカテコールに代謝されることが判明した。これらの代謝物は銅存在下で酸化的DNA損傷を起こした。生体内還元物質NADHの添加により、4-エチルカテコールによる酸化的DNA損傷は劇的に増強した。酸化的DNA損傷にはこれらの代謝物の酸化還元サイクルに伴い生成されるCu(I)と過酸化水素が関与することが明らかになった(Chem.Biol.Interact.2004)。これらの結果から、VOCの代謝物や光生成物などによる遺伝子損傷が、突然変異を介した発がんおよび免疫細胞の直接的な傷害による免疫能低下をもたらし、両者の相互作用が室内汚染物質による健康障害に関与すると考えられる。また我々は種々の環境発がん因子により生成される活性種がDNA損傷をもたらすことを明らかにし、研究報告を多数行っている。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (30 results)

All 2005 2004 Other

All Journal Article (18 results) Publications (12 results)

  • [Journal Article] 酸化ストレスの基礎 (3)酸化・ニトロ化ストレスとDNA傷害2005

    • Author(s)
      川西正祐
    • Journal Title

      臨牀消化器内科 肝と酸化ストレス 20(4)

      Pages: 421-429

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide2005

    • Author(s)
      Mizutani, H
    • Journal Title

      Life Sci. 76

      Pages: 1439-1453

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Amplification of C1027-induced DNA cleavage and apoptosis by a quiacrine-netropsin hybrid molecule in tumor cell lines2005

    • Author(s)
      Iwamoto, T
    • Journal Title

      Arch.Biochem.Biophys. 434

      Pages: 232-240

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanism of metal-mediated DNA damage induced by a metabolite of carcinogenic acetamide2004

    • Author(s)
      Sakano, K
    • Journal Title

      Chem.Biol.Interact. 149

      Pages: 52-59

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Oxidative DNA damage induced by a melatonin metabolite, 6-hydroxymelatonin, via a unique non-o-quinone type of redox2004

    • Author(s)
      Sakano, K
    • Journal Title

      Buiochem.Pharmacol. 68

      Pages: 1869-1878

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Copper-mediated oxidative DNA damage induced by eugenol : possible involvement of O-demethylation2004

    • Author(s)
      Sakano, K
    • Journal Title

      Mutat.Res. 565

      Pages: 35-44

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Repeated infection with Opisthorchis viverrini induces acculumulation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanine in the bile duct of hamsters via inducible nitric oxide synthase2004

    • Author(s)
      Pinlaor, S
    • Journal Title

      Carcinogenesis 25

      Pages: 1535-1542

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini : a model of inflammation-mediated carcinogenesis2004

    • Author(s)
      Pinlaor, S
    • Journal Title

      Nitric Oxide 11

      Pages: 175-183

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA dmage2004

    • Author(s)
      Midorikawa, K
    • Journal Title

      Chem.Biol.Interact. 150

      Pages: 271-281

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection2004

    • Author(s)
      Ma, N
    • Journal Title

      Biochem.Biphys.Res.Commun. 319

      Pages: 506-510

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Amplification of anticancer drug-induced DNA damage and apoptosis by DNA-binding compounds2004

    • Author(s)
      Kwanishi, S
    • Journal Title

      Curr.Med.Chem.Anti-Canc.Agents 4

      Pages: 415-419

    • Related Report
      2004 Annual Research Report
  • [Journal Article] DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect2004

    • Author(s)
      Iwamoto, T
    • Journal Title

      Cancer Sci. 95

      Pages: 454-458

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanism of carcinogenesis induced by a veterinary antimicrobial drug, nitrofurazone, via oxidative DNA damage and cell proliferation2004

    • Author(s)
      Hiraku, Y
    • Journal Title

      Cancer Lett. 215

      Pages: 141-150

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line

    • Author(s)
      Pinlaor, S
    • Journal Title

      Int.J.Parasitol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion

    • Author(s)
      Pinlaor, S
    • Journal Title

      World J.Gastroenterol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C

    • Author(s)
      Horiike, S
    • Journal Title

      J.Hepatol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] iNOS-dependent DNA damage in mouse model of inflammatory bowel disease

    • Author(s)
      Ding, X.
    • Journal Title

      Cancer Sci. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Guanine-specific DNA damage induced by gamma-irradiated histone

    • Author(s)
      Furukawa, A
    • Journal Title

      Biochem.J. (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Pinlaor, S: "Repeated infection with Opisthorchis viverrini induces accumulation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanine in the bile duct of hamsters via inducible nitric oxides synthase"Carcinogenesis. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwamoto, T: "DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and a role in its cytotoxic effect"Cancer Sci. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Toda, C: "DNA damage by ethylbenzenehydroperoxide formed from carcinogenic ethylbenzene by sunlight irradiation"Biochem.Biophys.Res.Commun.. 304. 638-642 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tada-Oikawa, S: "Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis"Life Sci.. 73. 3277-3288 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Pinlaor, S: "8-nitroguanine formation in the liver of hamsters infected with Opisthorchis viverrini"Biochem.Biophys.Res.Commun.. 309. 567-571 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakashima, S: "Vacuolar H(+)-ATPase Inhibitor Induce Apoptosis via Lysosomal Dysfunction in the Human Gastric Cancer Cell Line MKN-1"J.Biochem.. 134. 359-364 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwamoto, T: "Oxidative DNA damage induced by photodegradation products of 3(')-azido-3(')-deoxythymidine"Arch.Biochem.Biophys. 416. 155-163 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Furukawa, A: "(-)-Epigallocatechin gallate causes oxidative damage to isolated and cellular DNA"Biochem.Pharmacol.. 66. 1769-1778 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mizutani, H: "Distinct mechanisms of site-specific oxidative DNA damage by doxorubicin in the presence of copper(II) and NADPH-cytochrome P450 reductase"Cancer Sci.. 94. 686-691 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murata, M: "Oxidative DNA damage by hyperglycemia-related aldehydes and its marked enhancement by hydrogen peroxide"FEBS Lett.. 554. 138-142 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogawa, K: "Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu(II)"Mutat.Res.. 539. 145-155 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Seike, K: "Oxidative DNA damage induced by benz[a]anthracene metabolites via redox cycles of quinone and unique non-quinone"Chem.Res.Toxicol.. 16. 1470-1476 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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