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2000 Fiscal Year Final Research Report Summary

Metabolic activation of procarcinogens and cancer risk

Research Project

Project/Area Number 06280102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionHokkaido University

Principal Investigator

KAMATAKI Tetsuya  Laboratory of drug metabolism Hokkaido University Professor, 大学院・薬学研究科, 教授 (00009177)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Yoshiki  Hokkaido University, Assistant Professor, 大学院・薬学研究科, 助手 (80292019)
NAKAYAMA Kazuo  Hokkaido University, Assistant Professor, 大学院・薬学研究科, 助手 (20261323)
ARIYOSHI Noritaka  Hokkaido University, Associate Professor, 大学院・薬学研究科, 助教授 (00243957)
FUJITA Ken-ichi  Hokkaido University, Assistant Professor, 大学院・薬学研究科, 助手 (60281820)
Project Period (FY) 1999
KeywordsP450 / Salmonella typhimurium / Mutation assay / Metabolic activation / Genetic polymorphism / Lung cancer
Research Abstract

l. Ten strains of Salmonella typhimurium YG7108 expressing each form of human cytochrome P450 (CYP), CYP1A1, CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5, together with human NADPH-cytochrome P450 reductase (OR) have been established.
2. Mutagens were formed from promutagens such as aflatoxin B_1 and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone bv human CYP forms expressed in the established Salmonella cells.
3. 2-Phenylbenzotriazole derivatives, newly isolated from river water, are promutagens, were found to be activated by human CYP1A1 specifically.
4. Individuals carrying a whole deletion genotype of the CYP2A6 gene showed significantly less lung cancer risk.
5. Furthermore, it was found that the whole deletion of the CYP2A6 gene resulted in the low risk of small cell lung cancer and squamous cell lung cancer, which have been known to be caused associated with tobacco smoke.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] N.Ariyoshi, T.Kamataki et al.: "A high level expression of CYP2A in the lung of the Suncus (Suncus murinus) and its role in the Activation of 4-(methylntirosamino)-1-(3-pyridyl)-1-butanone (NNK)"Biochem.Biophys.Res.Commun.. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Fujita, T.Kamataki et al.: "Establishment of Salmonella strain expressing catalytically active human UDP-glucuronosyltransferase 1A1 (UGT1A1)."Life Sci.. (In press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takahashi, K.Nakayama, T.Kamataki et al.: "Cooperative regulation of CYP2C12 gene expression by signal transducer and activator of transcription 5 (STAT5) and liver-specific factor in female rats."J.Biol.Chem.. 274. 37117-37124 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Kamataki et al.: "CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of (+)-cis-3, 5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) in humans."J.Pharmacol.Exp.Ther.. 289. 437-442 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Ariyoshi, T.Kamataki et al.: "CYP2A6 gene deletion reduces susceptibility to lung cancer."Biochem.Biophys.Res.Commun.. 261. 658-660 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鎌滝哲也 他: "P450と多型、"呼吸器疾患の分子生物学""医学書院. 268-274 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鎌滝哲也 他: "第2章薬代謝、"現代医学の基礎・薬物動態と薬効""岩波書店(In press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Ariyoshi, T.Kamataki et al.: "A high level expression of CYP2A in the lung of the Suncus (Suncus murinus) and its role in the Activation of 4-(methylntirosamino)-1-(3-pyridyl)-1-butanone (NNK)"Biochem.Biophys.Res.Commun.. (In press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Fujita, T.Kamataki et al.: "Cooperative regulation of CYP2C12 gene expression by signal transducer and activator of transcription 5 (STAT5) and liver-specific factor in female rats."Life Sci.. (In press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Takahashi, K.Nakayama, T.Kamataki et al.: "Cooperative regulation of CYP2C12 gene expression by signal transducer and activator of transcription 5 (STAT5) and liver-specific factor in female rats."J.Biol.Chem.. 274. 37117-37124 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kamataki et al.: "CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) in humans."J.Pharmacol.Exp.Ther.. 289. 437-442 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Ariyoshi, T.Kamataki et al.: "CYP2A6 gene deletion reduces susceptibility to lung cancer."Biochem.Biophys.Res.Commun.. 261. 658-660 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kamataki et al.: "Characterization of a novel variant (S145C/L311V) of 3-hydroxysteroid/dihydrodiol dehydrogenase in human liver."Pharmacogenetics. 9. 763-771 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kamataki et al.: "Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene : effect on the CYP1A2 inducibility in humans."J.Biochem.. 125. 803-808 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Fujita, T.Kamataki et al.: "Inhibition of benzo[a]pyrene-induced mutagenesis by (-)-epigallocatechin gallate in the lung of rpsL transgenic mice."Carcinogenesis. 20. 421-424 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kamataki, and N.Ariyoshi: "P450 and its genetic polymorphism., in "Molecular Biology of Respiratory Diseases"."Igakushoin, ed.by Yoshikazu Kawakami, Naoyuki Taniguchi and Kozui Kita, Tokyo. 268-274 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kamataki: "Drug Metabolism, in "Drug Disposition and Action"."Iwanami-shoten, ed.by R.Kato and Y.Mizushima, In press, Tokyo. (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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