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環境因子の発がんリスク評価

Research Project

Project/Area Number 06280119
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionOsaka City University

Principal Investigator

福島 昭治  大阪市立大学, 医学部・第一病理学教室, 教授 (00137077)

Co-Investigator(Kenkyū-buntansha) 若林 敬二  国立がんセンター研究所, 生化学部, 部長 (60158582)
津田 洋幸  国立がんセンター研究所, 化学療法部, 部長 (10163809)
根本 信雄  富山医科薬科大学, 薬学部, 教授 (10085631)
佐藤 茂秋  神戸大学, 医学部・衛生学教室, 教授 (00076994)
高橋 道人  国立衛生試験所, 病理部, 部長 (30080005)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥110,500,000 (Direct Cost: ¥110,500,000)
Fiscal Year 1996: ¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 1995: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1994: ¥37,500,000 (Direct Cost: ¥37,500,000)
Keywords発がんリスク評価 / 環境因子 / ヘテロサイクリックアミン / 変異原性 / ニトロソ化合物 / 遺伝子変異 / DNA付加体 / 酸化的ストレス / 発がん性
Research Abstract

MeIQxについて全員の協力のもとに行った前年度の発がん実験における肝細胞の5-bromo-2'-deoxyuridine (BrdU)標識率を検索した。すなわち、肝細胞の増殖能が最も高い21日齢の雄性F344ラットを用い、0, 0.001, 0.01,0.1, 1,10ppmの低濃度域および100ppmのMeIQxを16週間連続投与した群におけるBrdU標識率はglutathione S-transferase placental form (GST-P)陽性細胞巣の出現とほぼ同様の曲線を示した。2)ラット肝発がんプロモーター,sodium phenobarbital (PB)は低濃度では肝GST-P陽性巣の発生を抑制し、PBの作用閾値の存在を再確認した。3) mutated allele specific amplification法はがん遺伝子の微少な変異を検出する方法としては不適当であることが判明した。4) IQとMeIQxの複合投与はその発がん性を増強した。5) PhIP-DNA付加体量には発がん標的臓器と非標的臓器の間に差はみられなかった。6)イニシエーション活性中期検索法におけるGST-P陽性細胞巣の発現程度は腫瘍発生と良く相関していた。7) p53ノックアウトマウスの膀胱発がん感受性はホモ欠失型>ヘテロ欠失型>野性型の順であった。8) lacI遺伝子導入マウスにおいて高濃度のMeIQxは発がん標的臓器にlacI変異頻度の上昇をもたらしたが、低濃度では上昇はみられなかった。9) quinolineとその誘導体の3-fluoroquinolineの発がん性はAmes試験の結果と良い相関性を示した。10) dimethylnitorsamineの低濃度域におけるラット肝発がんリスクの実験を班員全員の共同のもとに行っている。

Report

(3 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Wanibuchi, H., Fukushima, S. et al.: "Promoting effects of dimethylarsinic acid on N-buthyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in rats." Carcinogenesis. 17. 2435-2439 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ikezaki, S., Takahashi, M. et al.: "Chemopreventive effects of 24R, 25-dihydroxyvitamin D3, a vitamin D3 derivative, on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride." Cancer Res.56. 2767-2770 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakurai, J., Nemoto, N. et al.: "Maintenance and activation of Cyp2e-1 gene expression in mouse hepatocytes in primary culture." Biocim. Biophys. Acta,. 40. 1313-1335 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Uehara, N., Tsuda, H., et al.: "Decreased levels of 2-amino-3-methylimidazo [4, 5-f] quinoline-DNA-adducts in rats treated with b-carotene, a-tocopherol and freeze-dried aloe." Jpn. J. Cancer Res.87. 342-348 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Totsuka, Y., Wakabayashi, K., et al.: "Presence of N2-(deoxyguanosin-8-yl)-2-amino-3, 8-dimethylimidazo [4, 5-f] quinoxaline (dG-C8-MeIQx) in human tissues." Carcinogenesis. 17. 1029-1034 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kato, T., Nakae, D., et al.: "Dose-dependent induction of 8-hydroxyguanine and preneoplastic foci in rat liver by a food-derived carcinogen, 2-amino-3, 8-dimethylimidozo [4, 5-f] quinoxaline, at low dose levels." Jpn. J. Cancer Res.87. 127-133 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto,S.,Fukushima,S.et al.: "Cancer induction by an organic arsenic compound,dimethylarsinic acid(cacodylic acid),in F344/DuCrj rats after pretreatment with five carcinogens." Cancer Res.55. 1271-1276 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ogasawara,H.,Takahashi,M.et al.: "Urinary bladder carcinogenesis induced by melamine in F344 male rats:Correlation between carcinogenesis and urolith formation." Carcinogenesis. 16. 2773-2777 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nemoto,N.,et al.: "Maintenance of phenobarbital-inducible Cyp2b gene expression in C57BL/6 mouse hepatocytes in primary culture as spheroids." Arch.Biochem.Biophys.316. 362-369 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuda,H.et al.al.: "Cell proliferation and advancement of hepatocarcinogenesis in the rat are associated with a decrease in connexin 32 expression." Carcinogenesis. 16. 101-105 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tosuka,Y.,Wakabayashi,K.et al.: "Presence of N^2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(dG-C8-MeIQx)in human tissues." Carcinogenesis. in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] Hasegawa,R.,et al.: "Increased risk mammary carcinoma development following transplacental and trans-breast milk exposure to a food-derived carcinogen,2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine,in Sprague-Dawley rats." Cancer Res.55. 4333-4338 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takada,N.,Fukushima,S.,et.al.: "Enhancement by organosulfur compounds from garlic and onions of diethyl-nitrosamine-induced glutathione s-transferase positive foci in the rat liver." Cancer Res.54. 2895-2899 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takahashi,M.,et.al.: "Dose-dependent promoting effects of sodium chloride (NaCl) on rat glandular stomach carcinogenesis initiated with N-methyl-N′-nitro-N-nitrosoguanidine." Carcinogenesis. 15. 1429-1432 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,S.,Sato,S.,et.al.: "Methylthiouracil does not induce micronuclei in mouse reticulocytes." Mammalian Mutagenicity Study Group Communications. 2. 37-40 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nemoto,N.,et.al.: "Elevated expression of the Cypla2 gene in the presence of nicotinamide by adult mouse hepatocytes in primary culture." Arch.Biochem.Biophys.308. 292-298 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsuda,H.,et.al.: "Cell proliferation and advancement of hepatocarcinogenesis in the rat are associated with a decrease in connexin 32 expression." Carcinogenesis. 16. 101-105 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kushida,H.,Wakabayashi,K.,et.al.: "Dose-response study of MeIQx carcinogenicity in F344 male rats." Cancer Lett.83. 31-35 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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